CN207318405U - A kind of nano-pore detection device of modified biological probe - Google Patents
A kind of nano-pore detection device of modified biological probe Download PDFInfo
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- CN207318405U CN207318405U CN201721391647.7U CN201721391647U CN207318405U CN 207318405 U CN207318405 U CN 207318405U CN 201721391647 U CN201721391647 U CN 201721391647U CN 207318405 U CN207318405 U CN 207318405U
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Abstract
The utility model discloses a kind of nano-pore detection device of modified biological probe, including device body, described device body interior is provided with the first basalis, first basalis offers at least one micropore, along the axial direction of the micropore, the nano pore for being modified with probe is provided with the top of the micropore, the micropore bottom is provided with the second basalis with protein nano hole array.During detection, specific biomarkers can be captured by being modified with the nano pore of probe, produce specific curent change, by analyzing in curent change i.e. samples can be analyzed whether contain thing to be detected and concentration, by modifying specific bioprobe to nano pore, detection range is greatly expanded, and there is very high specificity and sensitivity, can be widely applied to the disease detection based on nano-pore technology and analysis.
Description
Technical field
The utility model belongs to nano-pore detection technique field, is related to a kind of nano-pore detection device, relates in particular to
A kind of nano-pore detection device for being modified with bioprobe.
Background technology
Nano-pore technology is a kind of new unimolecular detection technique, and the basic principle of nano-pore technology is：Nano-pore is located at
In the antiseepage film of two electrolyte liquor chambers, when voltage acts on electrolyte liquor chamber, the steady state ion electric current through hole is just formed, in aperture
The instant of ionic flux changes so that large biological molecule is distributed on film, therefore detects the electric current molecular recognition by aperture
It is possibly realized.Be electrolysed indoor charged molecule sample (such as DNA and protein) hole pass in and out or duct with nanometer scale on
Specific probe when combining, produce a series of fluctuations of ion current signal, the fluctuations of these signals reflect sample perhaps
More characteristics, such as molecular size, concentration and structure.Grasp the size, its surface characteristic, the voltage and electrolyte applied of nano-pore
Condition, it is possible to detect different types of biomolecule by suitably adjusting nano-pore.In the past decade, nano-pore technology has been
It is widely used in the research in terms of DNA sequencing, disease detection, drug screening and environmental monitoring.
Nano-pore can be divided into solid nano hole and biological nano hole, and biological nano hole refers to be present in various in organism
The nano-pore and nanochannel of various kinds, the protein channel of the nanotubes specifically formed in biological lipid film, they are
Connect biology interior and carry out energy, the approach of mass exchange with exterior.Solid nano hole be using physics, chemical method drilling or
The nano level passage for etching solid substrate to prepare.Wherein, biological nano hole is received in terms of modifiability and cost compared with solid-state
Metre hole tool has great advantage, but it has the problem of stability to test environment, electric current and noise requirements are higher.And consolidate
State nano-pore integrates aspect in stability, electric current, noise and technique significant advantage, but presently, there are and be difficult to what is modified
Technical bottleneck, while its cost is high.
At present, nano-pore technology has been achieved for some breakthrough progress in terms of applied to DNA sequencing, but in disease
Sick context of detection, during in face of complicated and diversified biological specimen, also without substantive breakthroughs, this is because lacking at present a kind of available
In the effective protein modified structure for catching relevant disease molecule, on the other hand current nano-pore detection technique not yet can be with
High-throughout nano-pore chip combines, so that Monitoring lower-cut is still higher, detection sensitivity is insufficient, and existing nanometer
Hole detection device volume is larger, inconvenient to carry.
Utility model content
For this reason, the technical problem to be solved by the utility model is to Conventional nano hole detection technique in terms of disease detection
Meet demand is still unable to, Monitoring lower-cut is higher, sensitivity is insufficient, and detection device is not portable, so as to propose that one kind can be used for disease
Disease detection, Monitoring lower-cut is low, high sensitivity, the nano-pore detection device and production method of portable modified biological probe.
In order to solve the above technical problems, the technical solution of the utility model is：
The utility model provides a kind of nano-pore detection device of modified biological probe, it includes device body, the dress
Put body interior and be provided with the first basalis, first basalis offers at least one micropore, along the axial direction of the micropore
The nano pore for being modified with probe is provided with the top of the micropore, the micropore bottom is provided with protein nano hole array
Second basalis.
Preferably, upper cell cavity is formed at the top of first basalis between described device body inner top surface, it is described on
Microfluidic module is provided with cell cavity.
Preferably, being provided with indicator electrode in the microfluidic module, voltage is provided with below first basalis
Electrode, the voltage electrode are corresponded with the micropore and set.
Preferably, the voltage electrode is connected to CMOS chip.
Preferably, the aperture of the micropore is 2-200 μm, the height of the micropore is 5-500 μm；The nano-pore battle array
The aperture of nano-pore is 1-100nm in row.
Preferably, the nano pore for being modified with probe is arranged at the 3rd basalis, the 3rd basalis is change
Learn polymer film.
Preferably, described device bodies top is further opened with liquid flow inlet and fluid outlet.
The above-mentioned technical proposal of the utility model has the following advantages compared with prior art：
(1) the nano-pore detection device of modified biological probe described in the utility model, including device body, described device
Body interior is provided with the first basalis, and first basalis offers at least one micropore, along the axial direction of the micropore, institute
State and the nano pore for being modified with probe is provided with the top of micropore, the micropore bottom is provided with the with protein nano hole array
Two basalises.During detection, specific biomarkers can be captured by being modified with the nano pore of probe, produced specific electric current and become
Change, it is special by being modified to nano pore by analyzing in curent change i.e. samples can be analyzed whether contain thing to be detected and concentration
Fixed bioprobe, greatly expands detection range, and has very high specificity and sensitivity, can be widely applied to be based on receiving
The disease detection of metre hole technology and analysis.
(2) the nano-pore detection device of modified biological probe described in the utility model, at the top of first basalis with
Upper cell cavity is formed between described device body inner top surface, the upper storage reservoir intracavitary is provided with microfluidic module.The microfluidic module
Available for replacing conducting liquid, form chemical polymerization thing film and embedded duct, liquid it is replaceable, expand detection device should
With scope, while reduce its use cost.
(3) the nano-pore detection device of modified biological probe described in the utility model, the microfluidic module is interior to be set
There is indicator electrode, voltage electrode is provided with below first basalis, the voltage electrode is corresponded with the micropore and set
Put, during detection, each micropore can be detected individually, greatly reduce Monitoring lower-cut, while have cheap testing cost with
And shorter detection time.
(4) production method of the nano-pore detection device of modified biological probe described in the utility model, including to albumen
Nano pore modification particular organisms probe, can be examined after the nano pore for being modified with bioprobe is prepared at the top of micropore
Survey, molecules detected can be evenly distributed at the top of each micropore, combined with the protein nano duct that probe is modified with micropore, produced
Raw specific signals, determine whether the concentration containing detectable substance and detectable substance, device preparation process by analyzing these signals
Simply, production cost is low, and obtained detection device detection range is wide, specificity and high sensitivity, the generally portable core of device
Laminated structure, is easy to carry about with one, and can be detected immediately.
Brief description of the drawings
In order to be more likely to be clearly understood the content of the utility model, below according to the specific implementation of the utility model
Example and with reference to attached drawing, is described in further detail the utility model, wherein
Fig. 1 is the nano-pore structure of the detecting device schematic diagram of the modified biological probe described in the utility model embodiment.
Reference numeral is expressed as in figure：1- device bodies；The first basalises of 2-；3- micropores；4- is modified with the nanometer of probe
Duct；The second basalises of 5-；6- indicator electrodes；The 3rd basalises of 7-；8- liquid flow inlets；9- fluid outlets；10- microfluid moulds
Block.
The utility model can be implemented with many different forms, should not be construed as limited to embodiment set forth herein,
Conversely, there is provided these embodiments so that the disclosure is thorough and complete, and the design of the utility model is fully conveyed to this
Field technology personnel, the utility model will be defined by the claims.In the accompanying drawings, for clarity, each device can be exaggerated
Size and relative size.Term " first ", " second " in the utility model specification and claims and attached drawing etc. are
For distinguishing similar object, without for describing specific order or precedence.It should be appreciated that the data so used
It can exchange in the appropriate case.In addition, term " comprising ", " having " and their any deformation, it is intended that covering is not
Exclusive includes.
Embodiment
Embodiment
The present embodiment provides a kind of nano-pore detection device of modified biological probe, it can be used for based on nano-pore technology
Disease detection and analysis, for the nano-pore detection device as shown in Figure 1, it includes device body 1, described device body 1 is interior
Portion is provided with the first basalis 2, first substrate according to the portable chip structure with accommodation space in described device body 1
Layer 2 is SU-8 photoresist base materials, and the micropore 3 that at least one aperture is 2-200 μm is offered on first basalis 2,
In the present embodiment, the aperture of the micropore 3 is 90 μm, and the height of micropore 3 is 5-500 μm, is 100 μm in the present embodiment, described
The quantity of micropore 3 is 500.The top of each micropore 3 is provided with the nano pore 4 for being modified with probe, the nano-pore
Road is protein nano duct, probe for can specific capture biomarker polypeptide, antibody, single-chain antibody or antibody variation
Area, the probe are arranged at the end or inside in the albumen duct.3 bottom of micropore is provided with the second basalis 5, and second
Base layer material is silicon and its derivative, graphene, aluminium oxide etc., and protein nano hole battle array is provided with second basalis 5
Row, in the protein nano hole array, the aperture of single nano-pore is 1-100nm, in the present embodiment, the aperture of the nano-pore
For 50nm, the distance between adjacent nano hole is 50-5000 μm, is 200 μm in the present embodiment.
Further, the space between the top of the first basalis 2 and the inner top surface of described device basic body 1 is formed
Cell cavity, the microporous space between the nano pore 4 for being modified with probe and second basalis 5 forms lower cell cavity, described
Upper storage reservoir intracavitary is provided with microfluidic module 10, and the microfluidic module 10 is used to replacing conducting liquid, in the microfluidic module
An indicator electrode 6 is provided with, the lower section of the first basalis 2 is provided with voltage electrode (not shown), the voltage electrode
Correspond and set with the micropore 3, each 3 bottom of micropore is provided with a voltage electrode, so that each micropore can
Individually to be detected, greatly reduce Monitoring lower-cut, improve detection sensitivity.The voltage electrode is also electrically coupled to CMOS cores
The software connection of piece, the CMOS chip and control unit, will carry out in the software of the signal transmission detected to control unit
Analysis.
Further, the nano pore 4 for being modified with probe is arranged at the 3rd basalis 7, the 3rd basalis 7
For chemical polymerization thing film layer.The top of described device body 1 is further opened with liquid flow inlet 8 and fluid outlet 9.
The present embodiment also provides a kind of production method of the nano-pore detection device of the modified biological probe, it is included such as
Lower step：
S1, to protein nano duct modified biological probe, can specific capture disease organism mark using protein fusion method
The probe amalgamation and expression of thing is remembered in the end or inside in the protein nano duct, and the probe can be can specific capture disease
Polypeptide, antibody, single-chain antibody or the antibody variable region of biomarker, such as can be repaiied NTA using the His labels of albumen end
The probe modification of decorations obtains being modified with the nano pore 4 of probe in albumen bore end.
S2, assemble nanometer hole detection device, are injected containing lipid or chemical poly from liquid flow inlet 8 into device body 1
The conducting solution of body, chemical multimer or matrix material can tile film forming behind the top of micropore 3, obtain the 3rd basalis 7, its
Signal can be detected by the CMOS chip and inspection software of electrode and connection；It is then injected into the modification obtained containing step S1
Have the conducting solution of the nano pore 4 of probe, when the single protein nano duct for being modified with probe be embedded into the 3rd basalis 7 with
Afterwards, limit more ducts by the direction and size that control voltage to be embedded in, each embedded egg for being modified with probe in the top of micropore 3
Detection device is obtained after white nano pore, can start to detect or preserve.
S3, detection sample, it would be desirable to which the biological sample of analysis injects described device body 1, biological sample by liquid flow inlet 8
Molecule is combined with being modified with the nano pore 4 of probe on micropore 3, produces nonspecific signal, by analyzing the nonspecific signal, analysis
Sample composition and concentration.
Wherein, protein nano duct is Phi29 connector albumen duct, SPP1, T3, T4, T5, T7 bacteriophage connector egg
One kind in Bai Kongdao, alpha-hemolysin, MspA albumen duct；The probe is polypeptide, antibody or antibody variable region
One kind.
Obviously, the above embodiments are merely examples for clarifying the description, and the restriction not to embodiment.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of change or
Change.There is no necessity and possibility to exhaust all the enbodiments.And the obvious change thus extended out or
Among the protection domain that variation is created still in the utility model.
Claims (7)
1. a kind of nano-pore detection device of modified biological probe, it is characterised in that including device body, in described device body
Portion is provided with the first basalis, and first basalis offers at least one micropore, is provided with and is modified with the top of the micropore
The nano pore of probe, the micropore bottom are provided with the second basalis with protein nano hole array.
2. the nano-pore detection device of modified biological probe according to claim 1, it is characterised in that first substrate
Upper cell cavity is formed between layer top and described device body inner top surface, the upper storage reservoir intracavitary is provided with microfluidic module.
3. the nano-pore detection device of modified biological probe according to claim 2, it is characterised in that the microfluid mould
Indicator electrode is provided with block, voltage electrode, the voltage electrode and the micropore one are provided with below first basalis
One is correspondingly arranged.
4. the nano-pore detection device of modified biological probe according to claim 3, it is characterised in that the voltage electrode
It is connected to CMOS chip.
5. according to the nano-pore detection device of claim 1-4 any one of them modified biological probes, it is characterised in that described
The aperture of micropore is 2-200 μm, and the height of the micropore is 5-500 μm；The aperture of nano-pore is 1- in the nanohole array
100nm。
6. the nano-pore detection device of modified biological probe according to claim 5, it is characterised in that described to be modified with spy
The nano pore of pin is arranged at the 3rd basalis, and the 3rd basalis is chemical polymerization thing film layer or lipid film layer.
7. the nano-pore detection device of modified biological probe according to claim 6, it is characterised in that described device body
Top is further opened with liquid flow inlet and fluid outlet.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201721391647.7U CN207318405U (en) | 2017-10-25 | 2017-10-25 | A kind of nano-pore detection device of modified biological probe |
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| CN201721391647.7U CN207318405U (en) | 2017-10-25 | 2017-10-25 | A kind of nano-pore detection device of modified biological probe |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109709185A (en) * | 2017-10-25 | 2019-05-03 | 深圳宣泽生物医药有限公司 | A kind of the nano-pore detection device and production method of modified biological probe |
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2017
- 2017-10-25 CN CN201721391647.7U patent/CN207318405U/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109709185A (en) * | 2017-10-25 | 2019-05-03 | 深圳宣泽生物医药有限公司 | A kind of the nano-pore detection device and production method of modified biological probe |
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| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180504 Termination date: 20191025 |