CN109164157A - The meagre film sensors of MOSFET type, detection system and detection method for biochemistry detection - Google Patents
The meagre film sensors of MOSFET type, detection system and detection method for biochemistry detection Download PDFInfo
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- CN109164157A CN109164157A CN201811260375.6A CN201811260375A CN109164157A CN 109164157 A CN109164157 A CN 109164157A CN 201811260375 A CN201811260375 A CN 201811260375A CN 109164157 A CN109164157 A CN 109164157A
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- 239000004411 aluminium Substances 0.000 claims description 6
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- -1 Antibody Proteins 0.000 claims description 3
- 108091007433 antigens Proteins 0.000 claims description 3
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- 235000020958 biotin Nutrition 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims 1
- 238000012544 monitoring process Methods 0.000 abstract description 4
- 238000003912 environmental pollution Methods 0.000 abstract description 3
- 235000013305 food Nutrition 0.000 abstract description 3
- 238000005259 measurement Methods 0.000 abstract description 3
- 108010057266 Type A Botulinum Toxins Proteins 0.000 description 8
- 229940094657 botulinum toxin type a Drugs 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000008267 milk Substances 0.000 description 5
- 210000004080 milk Anatomy 0.000 description 5
- 235000013336 milk Nutrition 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
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- 229910021641 deionized water Inorganic materials 0.000 description 4
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- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 3
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- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910003978 SiClx Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
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- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
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- 238000013399 early diagnosis Methods 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
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- 239000007924 injection Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
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- 238000003380 quartz crystal microbalance Methods 0.000 description 1
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- 238000010846 tandem mass spectrometry analysis Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4145—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4146—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS involving nanosized elements, e.g. nanotubes, nanowires
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4148—Integrated circuits therefor, e.g. fabricated by CMOS processing
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- Chemical & Material Sciences (AREA)
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- Microelectronics & Electronic Packaging (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Electrochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
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Abstract
The present invention provides a kind of meagre film sensors of MOSFET type, detection system and detection method for biochemistry detection, including the MOSFET export structure on substrate, the hollow-out part being arranged in substrate, the mems thin film in hollow-out part, four support micro-cantilevers, support micro-cantilever；Four support micro-cantilevers are symmetrically set, one end is connected with mems thin film, the other end is fixed after being connected with exterior base, and the MOSEFET export structure on four support micro-cantilevers is a pair of symmetrically arranged PMOS structure and a pair of symmetrically arranged NMOS structure.The present invention is easy to use, and sensor strong antijamming capability can guarantee measurement accuracy；MEMS processing and fabricating can be used in sensor, low in cost, and can guarantee that sensor has good consistency；The sensor and corresponding detection system are versatile, the detection and monitoring that can be used in the fields such as biomedicine, chemistry, food safety, environmental pollution.
Description
Technical field
The invention mainly relates to a kind of sensor technical fields for micro-nano-scale biochemistry detection, specially a kind of
The meagre film sensors of MOSFET type and detection system and detection method.The sensor and corresponding detection system can be used for giving birth to
Detection and monitoring in the fields such as object medicine, chemistry, food safety, environmental pollution.
Background technique
In terms of biochemistry detection, such as pathogen detection is based on antibody-antigen, the early diagnosis of cancer of aptamers, gas
Detection, heavy metal analysis etc. can be realized there are many method, common are liquid chromatogram, Tandem Mass Spectrometry Analysis, Enzyme-linked Immunosorbent Assay
Measurement etc..Such method takes time and effort, expensive.For this purpose, some new methods continue to bring out, as surface plasma is total
Vibration, quartz crystal microbalance, carbon nanotube, micro-cantilever etc..Micro-cantilever is because being higher than other inspections without label, detection sensitivity
Survey method has obtained extensive attention in last decade.The method that common micro-cantilever uses optical detection, i.e. micro-cantilever golden watch
When probe molecule on face occurs and specific reaction occurs for tested target molecule, micro-cantilever bending deformation can be made, be injected into micro-
It can also shift after the light beam reflection of cantilever beam gold surface, by this shifted signal of PSD units test, biochemistry can be obtained
The real time information of reaction.But the micro-cantilever detection system based on optical detection is there are many problems, as have in solution steam bubble or
Person's impurity, interference can be generated, opaque liquid cannot be detected etc..In addition, the micro-cantilever of optical read-out needed before use into
The complicated contraposition adjustment of row, it is time-consuming and laborious.To overcome disadvantages mentioned above, resistance pressure type micro-cantilever comes into being.But resistance pressure type is micro- outstanding
Arm beam is sensitive to environment temperature, and sensitivity is unable to reach the micro-cantilever of optical read-out.
Summary of the invention
For the deficiency for solving current technology, the present invention combination prior art provides a kind of for giving birth to from practical application
Change the meagre film sensors of MOSFET type, detection system and the detection method of detection, the sensor is easy to use, is applied to micro-nano
There is good precision in scale biochemistry detection field.
Technical scheme is as follows:
For the meagre film sensors of MOSFET type of biochemistry detection, including substrate, the hollow-out part being arranged in substrate, position
In in hollow-out part mems thin film, four support micro-cantilevers, support micro-cantilever on MOSFET export structure；
Four support micro-cantilevers are symmetrically set, and one end is connected with mems thin film, and the other end is connected with exterior base
After fix, the MOSEFET export structures on four support micro-cantilevers are a pair of symmetrically arranged PMOS structure and a pair of right
Claim the NMOS structure of setting.
The mems thin film composition is silicon or silica or silicon nitride, and less than 1.5 microns, mems thin film is positive meagre film thickness
It is rectangular or round.
The described four support micro-cantilevers for being used to support mems thin film are rectangle, and long generous size is micron level,
Supporting micro-cantilever composition is silicon or silica or silicon nitride.
MOSFET output metal electrodes on four supports micro-cantilever by silicon or silica or silicon nitride into
Row insulation-encapsulated.
The NMOS structure includes P-type silicon substrate, N-type drain D and source S, the grid G that polysilicon is constituted, drain D, source
The metal electrode that pole S and grid G are drawn is aluminium or gold, and carries out insulation processing by SiO2.
PMOS export structure includes N-type silicon base, p-type drain D and source S, the grid G that polysilicon doping WSix is constituted,
The metal electrode that drain D, source S and grid G are drawn is aluminium or gold, and carries out insulation processing by SiO2.
The meagre film sensors of MOSFET type are made of MEMS technology.
A kind of detection system using the meagre film sensors of MOSFET type,
The support micro-cantilever MOSFET of meagre film sensors exports NMOS1, PMOS1, NMOS2, PMOS2, wherein
NMOS1 grid grade meets positive voltage Vg, and drain electrode meets positive voltage VDD, and source level is connected to ground, output voltage V by resistance R1NMOS1；PMOS1
Grid grade meets negative voltage Vg, and drain electrode meets negative voltage-VDD, and source level is connected to ground, output voltage V by resistance R2PMOS1；
NMOS2 grid grade meets positive voltage Vg, and drain electrode meets positive voltage VDD, and source level is connected to ground by resistance R4, and output voltage is
VNMOS2；PMOS1 grid grade meets negative voltage Vg, and drain electrode meets negative voltage-VDD, and source level is connected to ground by resistance R3, and output voltage is
VPMOS2；
VNMOS1And VPMOS2Instrument amplifier IC1 is accessed, IC1 amplification factor is determined by Rg, VPMOS1And VNMOS2Access instrument is put
Big device IC2, IC2 amplification factor is determined that instrument amplifier output is summed by the summing circuit that IC3 is constituted by Rg, is exported
Final signal Vout。
A kind of detection method using the meagre film sensors of MOSFET type, when using meagre film sensors, to mems thin film
Single face carries out biochemical modification, to form specific probe molecule.
The biochemical molecule includes at least aptamers, antibody, antigen, DNA, biotin, gas, moisture content.
Beneficial effects of the present invention:
The present invention is by the contact surface of sensor mems thin film external information in response, on the mems thin film after biochemical modification
When specific reaction occurs for probe molecule and tested target molecule, sensor mems thin film can be made to deform, i.e., it is convex or recessed, from
And four connection micro-cantilevers for supporting sensor mems thin film is made to bend, micro-cantilever deflection of beam can make MOSFET output hair
It is raw to change, by subsequent process circuit, signal is acquired in real time, realizes the real-time monitoring to Biochemical Information, it is whole easy to use, it passes
Sensor strong antijamming capability can guarantee measurement accuracy；MEMS processing and fabricating can be used in sensor, low in cost, and can protect
Demonstrate,proving sensor has good consistency；The sensor and corresponding detection system are versatile, can be used for biomedical, change
Detection and monitoring in the fields such as, food safety, environmental pollution.
Detailed description of the invention
Attached drawing 1 is the meagre film sensors front schematic view of MOSFET type.
Attached drawing 2 is NMOS export structure schematic diagram.
Attached drawing 3 is PMOS export structure schematic diagram.
Attached drawing 4 is NMOS, PMOS complementary type output circuit figure.
Fig. 5 is NMOS output characteristic curve.
Fig. 6 is PMOS output characteristic curve.
Fig. 7 is liquid biochemical detection device figure.
Fig. 8 is liquid biochemistry detection response curve.
Fig. 9 is gas-detecting device figure.
Figure 10 is that sensor discharges gas concentration real-time response curve to VRLA battery.
Figure 11 is that sensor output voltage and VRLA battery discharge gas concentration corresponding relationship.
Specific embodiment
With reference to the drawings and specific embodiments, the invention will be further described.It should be understood that these embodiments are merely to illustrate
The present invention rather than limit the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, this field
Technical staff can make various changes or modifications the present invention, and such equivalent forms equally fall within range defined herein.
As shown in Figure 1, the meagre film sensors of MOSFET type processed by MEMS processing technology include SOI substrate 11, engrave
Empty part 12, rectangular mems thin film 13 (or round mems thin film 17), support micro-cantilever 15, four support micro-cantilevers 15 are mutual
Symmetrically, one end is connected with mems thin film 13 or 17, and the other end is fixed to be connected with external silicon base 11, supports on micro-cantilever 15
MOSFET exports PMOS structure 14 and NMOS structure 16 is in pairs and symmetrical.
(or 17) composition of mems thin film 13 is silicon or silica or silicon nitride.13 thickness of mems thin film is less than 1.5 microns.
Four support micro-cantilevers 15 for being used to support mems thin film 13 are rectangle, and long generous size is micron level.
Supporting 15 composition of micro-cantilever is silicon or silica or silicon nitride.
Supporting the MOSFET export structure on micro-cantilever 15 is complementary structure, i.e., a pair is pmos type, another pair is
NMOS type.
As shown in Fig. 2, NMOS export structure 16 includes P-type silicon substrate, N-type drain D and source S, the grid that polysilicon is constituted
Pole G, the metal electrode that drain D, source S and grid G are drawn is aluminium or gold, and carries out insulation processing by SiO2.
As shown in figure 3, PMOS export structure 14 includes N-type silicon base, p-type drain D and source S, polysilicon doping WSix
The grid G of composition, the metal electrode that drain D, source S and grid G are drawn is aluminium or gold, and carries out insulation position by SiO2
Reason.
PMOS, NMOS internal structure are including but not limited to structure shown in Fig. 2, Fig. 3.
As shown in figure 4, support micro-cantilever MOSFET exports NMOS1, PMOS1, NMOS2, PMOS2.NMOS1 grid grade connects just
Voltage Vg, drain electrode meet positive voltage VDD, and source level is connected to ground, output voltage V by resistance R1NMOS1；PMOS1 grid grade connects negative voltage
Vg, drain electrode meet negative voltage-VDD, and source level is connected to ground, output voltage V by resistance R2PMOS1。
NMOS2 grid grade meets positive voltage Vg, and drain electrode meets positive voltage VDD, and source level is connected to ground by resistance R4, and output voltage is
VNMOS2；PMOS1 grid grade meets negative voltage Vg, and drain electrode meets negative voltage-VDD, and source level is connected to ground by resistance R3, and output voltage is
VPMOS2。
VNMOS1And VPMOS2Instrument amplifier IC1 is accessed, IC1 amplification factor is determined by Rg, VPMOS1And VNMOS2Access instrument is put
Big device IC2, IC2 amplification factor is determined that instrument amplifier output is summed by the summing circuit that IC3 is constituted by Rg, is exported
Final signal Vout。
Fig. 5, Fig. 6 are respectively NMOS, PMOS output characteristic curve.
Biochemical modification is carried out to the single face of mems thin film (front or back) when in use.Such as, meagre film surface is nitrogen
When SiClx, make mems thin film surface amination using APTES reagent, by biomolecule such as antibody by way of self assembly (SAM)
It is combined with it, form specific probe molecule.
The biomolecule is including but not limited to aptamers, antibody, antigen, DNA, biotin etc..
The present invention is described further in terms of biochemistry detection combined with specific embodiments below, but is not limited to this implementation
Example.
Detection of the meagre film sensors of embodiment 1:MOSFET type to botulinum toxin type A
As shown in fig. 7, the meagre film sensors 24 of MOSFET type are connected with circuit board 25,25 are connected with PC machine 27, injection
Pump 21,26 is connected with container 22, and temperature controller 23 is adhered to 22 bottom of container.
With acetone, dehydrated alcohol, the deionized water successively meagre film surface of cleaning sensor, then with H2O2/H2SO4 (1:3)
Solution drops to the meagre film surface of sensor, successively cleans multipass with dehydrated alcohol, deionized water after 2 minutes, and with being dried with nitrogen；
3- aminopropyl triethoxysilane (APTES) ethanol solution is instilled into container, 3 hours is placed at room temperature for and makees silanization treatment,
It is multiple with deionized water cleaning container；Glutaraldehyde solution is injected into container and is placed at room temperature for 3 hours, with deionized water cleaning container
Repeatedly.
By phosphate buffer (PBS) the buffering drop of botulinum toxin type A antibody in the sensor mems thin film modified
Surface, whole container are placed 1 hour under 37 DEG C of isoperibols.With phosphate buffer (pH 7.4) to sensor and entire appearance
Device is cleaned, and unreacted antibody is removed.Bovine serum albumin(BSA) (BSA, 0.05%w/v) is not involved in sensor to the portion of reaction
Divide and purify within 1 hour.
The milk of botulinum toxin type A will be free of, botulinum toxin type A content is respectively that the milk of 10ng/ml and 20ng/ml exists
It is injected separately into container 22 under the same terms with syringe pump.Mems thin film is in the botulinum toxin type A milk-based liq of different depth
Different degrees of protrusion occurs, output signal is caused to change.
As shown in figure 8, three output voltage signal curves respectively correspond plain chocolate, botulinum toxin type A content is 10ng/ml
With the milk of 20ng/ml, the i.e. corresponding curve difference of the botulinum toxin type A of various concentration.It is by botulinum toxin type A content
The output voltage signal curve that the corresponding output voltage signal curve of the milk of 10ng/ml and 20ng/ml subtracts plain chocolate is
The variable signal of actual concentrations.
Embodiment 2:VRLA battery discharges gas detection
As shown in figure 9, the meagre film sensors 38 of MOSFET type are connected by conducting wire 36 with circuit board 39, circuit board 39 and
PC machine 310 is connected, and sensor 38 is placed in sealing container 37.For storing the container 31 and storage VRLA battery of pure air
The container 32 for discharging gas is mixed by control valve 33,34 respectively, is sent into sealing container 37 by glass tube 35.Pass through control
The concentration of VRLA battery release gas in sealing container 37 can be changed in the turn-on time of valve 33,34.
Control valve 33,34 when experiment, adjust ratio of the VRLA battery release gas in 37 containers, and ratio is respectively
20%, 30%, 40%, 70%, 80%.Figure 10 is different proportion real-time response curve, and Figure 11 is the response curve according to Figure 10
The fitting result of progress, because of manual control valve 33, there are certain errors for 34 adjusting ratios, but remain to the preferable linear pass of reaction
System.
Claims (10)
1. being used for the meagre film sensors of MOSFET type of biochemistry detection, it is characterised in that: including substrate, engraving in substrate is arranged in
Empty part, four support micro-cantilevers, supports the MOSFET on micro-cantilever to export knot at the mems thin film in hollow-out part
Structure；
Four support micro-cantilevers are symmetrically set, and one end is connected with mems thin film, and the other end is solid after being connected with exterior base
Fixed, the MOSEFET export structure on four support micro-cantilevers is that a pair of symmetrically arranged PMOS structure and a pair are symmetrically set
The NMOS structure set.
2. being used for the meagre film sensors of MOSFET type of biochemistry detection as described in claim 1, it is characterised in that: described meagre
Film composition is silicon or silica or silicon nitride, and meagre film thickness is square less than 1.5 microns, mems thin film or circle.
3. being used for the meagre film sensors of MOSFET type of biochemistry detection as described in claim 1, it is characterised in that: described four
The support micro-cantilever for being used to support mems thin film is rectangle, and long generous size is micron level, supports micro-cantilever composition
For silicon or silica or silicon nitride.
4. being used for the meagre film sensors of MOSFET type of biochemistry detection as described in claim 1, it is characterised in that: described four
The MOSFET output metal electrode on micro-cantilever is supported to carry out insulation-encapsulated by silicon or silica or silicon nitride.
5. being used for the meagre film sensors of MOSFET type of biochemistry detection as described in claim 1, it is characterised in that: the NMOS
Structure includes P-type silicon substrate, N-type drain D and source S, the grid G that polysilicon is constituted, what drain D, source S and grid G were drawn
Metal electrode is aluminium or gold, and carries out insulation processing by SiO2.
6. being used for the meagre film sensors of MOSFET type of biochemistry detection as described in claim 1, it is characterised in that: PMOS output
Structure includes N-type silicon base, p-type drain D and source S, the grid G that polysilicon doping WSix is constituted, drain D, source S and grid
The metal electrode that G is drawn is aluminium or gold, and carries out insulation processing by SiO2.
7. being used for the meagre film sensors of MOSFET type of biochemistry detection as described in claim 1, it is characterised in that: described
The meagre film sensors of MOSFET type are made of MEMS technology.
8. a kind of detection system using any one of the claim 1~6 meagre film sensors of MOSFET type, feature exist
In:
The support micro-cantilever MOSFET of meagre film sensors exports NMOS1, PMOS1, NMOS2, PMOS2, wherein NMOS1 grid
Grade meets positive voltage Vg, and drain electrode meets positive voltage VDD, and source level is connected to ground, output voltage V by resistance R1NMOS1；PMOS1 grid grade connects
Negative voltage Vg, drain electrode meet negative voltage-VDD, and source level is connected to ground, output voltage V by resistance R2PMOS1；
NMOS2 grid grade meets positive voltage Vg, and drain electrode meets positive voltage VDD, and source level is connected to ground, output voltage V by resistance R4NMOS2；
PMOS1 grid grade meets negative voltage Vg, and drain electrode meets negative voltage-VDD, and source level is connected to ground, output voltage V by resistance R3PMOS2；
VNMOS1And VPMOS2Instrument amplifier IC1 is accessed, IC1 amplification factor is determined by Rg, VPMOS1And VNMOS2Access instrument amplifier
IC2, IC2 amplification factor are determined that instrument amplifier output is summed by the summing circuit that IC3 is constituted, and output is final by Rg
Signal Vout。
9. a kind of detection method using any one of the claim 1~6 meagre film sensors of MOSFET type, feature exist
In: when using meagre film sensors, biochemical modification is carried out to the single face of mems thin film, to form specific probe molecule.
10. detection method as claimed in claim 8, it is characterised in that: the biochemical molecule include at least aptamers,
Antibody, antigen, DNA, biotin, gas, moisture content.
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Application publication date: 20190108 Assignee: Ningbo Falizhi Skincare Products Co.,Ltd. Assignor: ZHEJIANG NORMAL University Contract record no.: X2024980000667 Denomination of invention: Detection system for biochemical testing Granted publication date: 20201225 License type: Common License Record date: 20240115 |