CN115178313A - Design method of hollow micro-nano composite beam for biochemical molecule detection - Google Patents
Design method of hollow micro-nano composite beam for biochemical molecule detection Download PDFInfo
- Publication number
- CN115178313A CN115178313A CN202210934979.4A CN202210934979A CN115178313A CN 115178313 A CN115178313 A CN 115178313A CN 202210934979 A CN202210934979 A CN 202210934979A CN 115178313 A CN115178313 A CN 115178313A
- Authority
- CN
- China
- Prior art keywords
- micro
- detection
- reaction
- composite beam
- liquid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000001514 detection method Methods 0.000 title claims abstract description 57
- 238000000034 method Methods 0.000 title claims abstract description 33
- 239000002114 nanocomposite Substances 0.000 title claims abstract description 24
- 238000013461 design Methods 0.000 title claims abstract description 14
- 239000007788 liquid Substances 0.000 claims abstract description 46
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 14
- 239000010703 silicon Substances 0.000 claims abstract description 14
- 238000011065 in-situ storage Methods 0.000 claims abstract description 13
- 230000008859 change Effects 0.000 claims abstract description 10
- 239000000126 substance Substances 0.000 claims abstract description 10
- 150000003377 silicon compounds Chemical class 0.000 claims abstract description 9
- 239000000758 substrate Substances 0.000 claims abstract description 9
- 230000035945 sensitivity Effects 0.000 claims abstract description 8
- 239000010409 thin film Substances 0.000 claims abstract description 7
- 238000002955 isolation Methods 0.000 claims abstract description 4
- 239000000463 material Substances 0.000 claims abstract description 4
- 239000002131 composite material Substances 0.000 claims description 16
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000005530 etching Methods 0.000 claims description 11
- 238000011897 real-time detection Methods 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 238000013016 damping Methods 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- 238000005842 biochemical reaction Methods 0.000 claims description 4
- 238000004140 cleaning Methods 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 239000002086 nanomaterial Substances 0.000 claims description 4
- 239000011521 glass Substances 0.000 claims description 3
- 238000000465 moulding Methods 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 238000001179 sorption measurement Methods 0.000 claims description 3
- 230000009286 beneficial effect Effects 0.000 claims description 2
- 238000002474 experimental method Methods 0.000 claims description 2
- 239000012780 transparent material Substances 0.000 claims description 2
- 239000002699 waste material Substances 0.000 claims description 2
- 238000001039 wet etching Methods 0.000 claims description 2
- 238000001459 lithography Methods 0.000 claims 1
- 239000010408 film Substances 0.000 abstract description 6
- 238000003889 chemical engineering Methods 0.000 abstract description 2
- 238000013329 compounding Methods 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 1
- 238000005516 engineering process Methods 0.000 description 7
- 230000008901 benefit Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001259 photo etching Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 230000036046 immunoreaction Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00134—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems comprising flexible or deformable structures
- B81C1/0015—Cantilevers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5302—Apparatus specially adapted for immunological test procedures
- G01N33/5304—Reaction vessels, e.g. agglutination plates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0896—Nanoscaled
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Manufacturing & Machinery (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Dispersion Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Abstract
The invention discloses a design method of a hollow micro-nano composite beam for biochemical molecule detection. The beam is formed by compounding two structural materials, namely a silicon or silicon compound substrate and a flexible film. A liquid sample inlet, a liquid sample outlet, a liquid sample inlet microchannel, a liquid sample outlet microchannel and a sample reaction tank to be detected are arranged between the flexible thin film layer and the silicon or silicon compound substrate layer, and the reaction tank is positioned in a mass sensitive area of the beam. The method provides a liquid reaction-vacuum detection mode, the object to be detected is absorbed in the micro flow channel, the whole structure is placed in a vacuum environment, and the detection mode can realize effective isolation of the reaction environment and the detection environment. The high sensitivity of biochemical molecules and the in-situ real-time rapid detection are completed by detecting the frequency change caused by the reaction of the substance to be detected, and the method can be widely applied to the engineering fields of medicine, chemical engineering and the like.
Description
Technical Field
The invention relates to the fields of MEMS, biomedicine and chemical engineering, in particular to a design method of a hollow micro-nano composite beam for biochemical molecule detection.
Background
With the cross fusion of electronic information technology and high and new technologies such as biotechnology, micro electro mechanical system technology and nanotechnology, various novel micro-nano biosensors are emerging in recent years [1]. Among them, the mass-sensitive beam structure sensor based on MEMS becomes one of the most potential devices in the field of biochemical detection due to its advantages of small size, simple structure, high sensitivity, easy array and integration [2 ]. It has two working modes as a biochemical sensor: static mode and dynamic mode. That is, when the substance to be detected is specifically adsorbed on the functionalized beam, the deflection or resonance frequency of the beam is changed, and the quality or quantity of the substance to be detected adsorbed on the beam can be reflected by detecting the change optically or electrically.
For liquid biochemical molecule detection, most of the research focuses on two ways, one is drying after liquid reaction is completed, which cannot realize in-situ real-time detection in liquid environment and can reduce the activity of biomolecules after drying [3 ]]The accuracy of the detection is reduced. The other method is to soak the micro-cantilever in a liquid flow cell for reaction, although the method can realize the in-situ real-time measurement of biochemical molecules, when a sample is detected in the flow cell, the micro-cantilever is in a liquid detection environment, the damping influence is large, and the quality factor is reduced sharply (10) 2 Below) so that the detection sensitivity is greatly reduced [ 4)]Limiting its high precision applications. In the recent research of Cambridge university, a microfluidic chip made of PDMS is used to mix a serum sample to be detected with nitrogen into aerosol, and the aerosol is quantitatively dropped on a micro beam for detection, so that most of moisture in the sample is rapidly volatilized, and only molecules to be detected are left to react with a sensitive layer [5 ]]Micro suspensionThe arm beam is isolated from the liquid reaction environment, has the advantage of high sensitivity of gas environment detection, but still does not realize in-situ real-time monitoring. Based on the defects of the above detection modes, it is urgently needed to provide a beam structure which is isolated from a liquid environment and can carry out real-time in-situ detection.
Reference to the literature
[1]P.Teerapanich，M.Pugnière，C.Henriquet，Y.L.Lin，C.F.Chou，and T.
″Nanofluidic Fluorescence Microscopy(NFM)for real-time monitoring of protein binding kinetics and affinitystudies，″Biosensors&Bioelectronics，vol.88，pp.25-33，2017.
[2]A.Boisen，S.Dohn，S.S.Keller，S.Schmid，and M.Tenje，″Cantilever-like micromechanical sensors，″Reports on Progress in Physics，vol.74，pp.036101，2011.
[3]E.Timurdogan，B.E.Alaca，I.H.Kavakli，and H.Urey，″MEMS biosensor for detection of Hepatitis A and C viruses in serum，″Biosensors&Bioelectronics，vol.28，pp.189-194，2011.
[4]J.Tamayo，A.D.Humphris，A.M.Malloy，and M.J.Miles，″Chemical sensors and biosensors in liquid environment based on microcantilevers with amplified quality factor，″Ultramicroscopy，vol.86，pp.167-173，2001.
[5]T.Kartanas，V.Ostanin，P.K.Challa，R.Daly，J.Charmet，and T.P.J.Knowles，″Enhanced Quality Factor Label-free Biosensing with Micro-Cantilevers Integrated into Microfluidic Systems，″Analytical Chemistry，vol.89，pp.11929-11936，2017.
Disclosure of Invention
Technical problem to be solved
In order to realize high-sensitivity in-situ real-time detection of a substance to be detected, technical breakthroughs are needed in the aspects of high-sensitivity frequency detection, in-situ real-time detection, reduction of damping of a detection environment and the like. The invention provides a design method of a hollow micro-nano composite beam for biochemical molecule detection, which is formed by bonding two materials, namely a silicon or silicon compound substrate layer and a flexible thin film layer, and adopts a liquid reaction-vacuum detection method, so that the damping brought by a liquid environment is effectively avoided, and the aim of real-time in-situ detection can be achieved.
(II) technical scheme
In order to realize high-sensitivity and in-situ real-time detection of biochemical molecules to be detected, the invention provides a design method of a hollow micro-nano composite beam for biochemical molecule detection. A liquid sample inlet, a liquid sample outlet, a liquid sample inlet micro-channel and a liquid sample outlet micro-channel are carved between the flexible film and the silicon or silicon compound substrate. Etching reaction cells in the mass sensitive area of the beam for biochemical reactions.
According to the scheme, the composite beam is prepared by the following process steps of etching the external integral structure of the beam on an SOI or silicon chip, and then carrying out secondary photoetching and etching to form an internal hollow micro-nano structure so as to obtain the lower thin layer of the composite beam. And (3) selecting a glass sheet to etch the flexible film, or adopting a technology of reverse molding on a hard template to form an upper thin layer of the composite beam structure. The flexible film of the upper thin layer is made of transparent materials, and optical observation and detection before and after reaction in the reaction tank are facilitated. And then bonding the upper and lower thin layers. And finally, releasing the sacrificial layer by adopting a deep silicon etching technology and an organic matter wet etching technology to obtain the hollow composite beam structure.
In the scheme, the hollow micro-nano structure composite beam adopts a liquid reaction-vacuum detection mode to reduce the influence of liquid environment damping on sensitivity and quality factor to the maximum extent, and the detection mode can realize effective isolation of a reaction environment and a detection environment and complete in-situ real-time detection of a substance to be detected.
In the above scheme, the substance to be detected is injected into the micro-channel inside the beam through the liquid inlet, the injected micro-fluid can generate a certain effect on the beam, and the aim of detecting the quality or quantity of the biological molecules in the micro-fluid is achieved by detecting the offset of the free end of the beam or the change of the resonance frequency of the beam.
In the scheme, the reaction tank is used for locally modifying the sensitive layer, so that the reaction between the sensitive layer and the target molecule is generated in the mass sensitive area of the beam, and the sample to be detected can cause the peak value of deflection or frequency change when flowing through the mass sensitive area of the beam. Meanwhile, the method reduces the influence of large-area adsorption on the beam elastic constant, and can effectively improve the detection precision of the hollow micro-nano composite beam sensor.
In the scheme, the hollow micro-nano composite beam structure can adopt an array form, different sensitive layers are modified in reaction tanks of different beams, so that simultaneous detection of various objects to be detected can be realized, and the manufacturing cost is saved to a certain extent. And after an experiment is carried out, cleaning liquid is injected through the liquid inlet, and cleaning waste liquid is discharged through the liquid outlet, so that the beam can be cleaned simply and in a pollution-free manner.
In the above scheme, the beam structure includes, but is not limited to, a rectangular micro-cantilever beam, a T-shaped micro-cantilever beam, a circular micro-cantilever beam, a triangular micro-cantilever beam, a U-shaped micro-cantilever beam, and a double-end clamped beam.
(II) advantageous effects
According to the technical scheme, the invention has the beneficial effects that:
1. the design method of the hollow micro-nano composite beam for biochemical molecule detection provided by the invention realizes effective isolation of an immunoreaction environment and a beam test environment by a detection mechanism of internal fluid and external vacuum, greatly reduces the influence of an external environment, and improves the detection sensitivity.
2. According to the design method of the hollow micro-nano composite beam for biochemical molecule detection, provided by the invention, the reaction tank structure is etched in the mass sensitive area of the beam, so that large-area adsorption is reduced, and the amount deflection or frequency change relatively reaches the peak value.
3. According to the design method of the hollow micro-nano composite beam for biochemical molecule detection, provided by the invention, through researching a high-sensitivity sensing mechanism of the sensor and an application mechanism in joint inspection of markers, a new method for in-situ real-time monitoring of molecular dynamics in a liquid environment is discovered, a theoretical basis is provided for obtaining the geometric structure design of a high-performance composite beam sensor and the surface functionalization process of biochemical substances, a means is provided for manufacturing a novel composite beam array sensor which is low in cost, portable and rapid in detection, and the method has important application value.
Drawings
Fig. 1 is a schematic diagram of a hollow micro-nano composite beam structure for biochemical molecular detection according to an embodiment of the present invention (taking a rectangular micro-cantilever as an example);
fig. 2 is a schematic cross-sectional view of a hollow micro-nano composite beam structure for biochemical molecule detection (taking a rectangular micro-cantilever as an example).
Fig. 3 is a process flow diagram for manufacturing a rectangular hollow micro-nano composite beam, wherein the preparation of the flexible layer is performed by etching on a glass plate, and in addition, the flexible layer can be manufactured by adopting methods such as reverse molding.
FIG. 4 is some other beam structures than a rectangular micro-cantilever, (a) a T-shaped micro-cantilever; (b) a circular micro-cantilever; (c) a triangular micro-cantilever; (d) a U-shaped micro-cantilever; and (e) fixing and supporting the beam at the two ends.
Description of reference numerals:
1. bulk silicon; 2. an oxygen burying layer; 3. a silicon or silicon compound substrate; 4. a flexible film; 5. a liquid inlet/outlet; 6. liquid inlet/outlet microchannels; 7. and (4) a reaction tank.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to specific embodiments and the accompanying drawings.
Fig. 1 is a schematic diagram of a hollow micro-nano composite beam structure for biochemical molecular detection according to an embodiment of the present invention, which is taken as an example of a rectangular micro-cantilever, and fig. 2 is a cross-sectional diagram of fig. 1. The composite structure includes a beam body and a hollow microchannel for biochemical reactions. Wherein the beam main body is formed by compounding two structural materials of a silicon or silicon compound substrate and a flexible film. A liquid sample inlet, a liquid sample outlet, a liquid sample inlet micro-channel and a liquid sample outlet micro-channel are arranged between the flexible thin film layer and the silicon or silicon compound substrate layer, and the mass sensitive area of the beam is an etching reaction tank. Fig. 3 is a flow chart of a manufacturing process of the hollow micro-nano composite beam, a lower thin layer of the composite micro-cantilever beam is obtained through photoetching and etching, and an upper thin layer of the micro-cantilever beam composite structure is formed by utilizing the etching or reverse mould technology on a hard template. And then bonding the upper and lower thin layers, and finally releasing the sacrificial layer to obtain the hollow composite micro-cantilever structure. Fig. 4 shows some other beam structures except the rectangular micro-cantilever, and the composite beam of these structures can effectively isolate the molecule to be detected from the external environment by using the liquid reaction-vacuum detection method, thereby realizing high sensitivity and in-situ real-time detection of the biochemical molecule to be detected.
In practical application, the sensitive layer specifically combined with the object to be detected is modified in the reaction tank, the object to be detected flows into the reaction tank from the liquid sample inlet through the sample injection microchannel, and after the reaction is finished, the reacted sample is taken out from the sample outlet microchannel and the sample outlet on the other side. The beam can be driven in a piezoelectric excitation mode in a dynamic working mode, the resonant frequency before and after the reaction of the object to be measured and the sensitive layer is respectively measured, and the frequency change is measured by a Wheatstone bridge detection circuit. In the static mode detection, an optical detection method can be adopted, and the bending change of the micro-cantilever can be reflected through the beam deflection on the position sensitive detector. The information such as the mass or the quantity of the adsorbed biochemical molecules can be obtained through the difference between the two frequencies or the change of the deflection quantity
In order to realize the simultaneous detection of various biochemical molecules, a plurality of beam structures shown in fig. 1 can be integrated together to manufacture a beam array, one of the beam structures is selected as a reference beam, and the rest beams can be used for modifying different objects to be detected, so that the simultaneous detection of various biochemical molecules can be realized.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are only exemplary embodiments of the present invention, and are not intended to limit the present invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. A design method of a hollow micro-nano composite beam for biochemical molecule detection is characterized in that a design structure provided by the method comprises a beam and a hollow micro-channel for biochemical reaction, wherein the beam is composed of two materials of a silicon or silicon compound substrate layer and a flexible thin film layer, a liquid sample inlet, a liquid sample outlet, a liquid sample inlet micro-channel and a liquid sample outlet micro-channel are carved between the flexible thin film and the silicon or silicon compound substrate, and a mass sensitive area of the beam is etched to form a reaction tank for biochemical reaction and increase the reaction area.
2. The method for designing a hollow micro-nano composite beam for biochemical molecule detection according to claim 1, wherein the method comprises the following steps of etching an external integral structure of the beam on an SOI or silicon wafer, performing secondary lithography and etching to form an internal hollow micro-nano structure, obtaining a lower thin layer of the composite beam, selecting a glass wafer to etch the flexible thin film, or forming an upper thin layer of the composite beam structure by a reverse molding technique on a hard template, wherein the flexible thin film of the upper thin layer is made of a transparent material, which is beneficial to optical observation and detection before and after reaction in a reaction tank, bonding the upper thin layer and the lower thin layer, and finally releasing a sacrificial layer by a deep silicon etching technique and an organic wet etching technique to obtain the hollow composite beam structure.
3. The method for designing the hollow micro-nano composite beam for biochemical molecule detection according to claim 1, wherein the hollow micro-nano structure composite beam adopts a liquid reaction-vacuum detection mode to reduce the influence of liquid environment damping on sensitivity and quality factor to the maximum extent, and the detection mode can realize effective isolation of a reaction environment and a detection environment and complete in-situ real-time detection of a substance to be detected.
4. The design method of the hollow micro-nano composite beam for biochemical molecule detection according to claim 1, characterized in that a substance to be detected is injected into the micro-channel of the beam through the liquid inlet, the injected micro-fluid can generate a certain effect on the beam, and the mass or the quantity of the biological molecules in the micro-fluid can be detected by detecting the offset of the free end of the beam or the change of the resonance frequency of the beam.
5. The method for designing the hollow micro-nano composite beam for biochemical molecule detection according to claim 1, wherein the reaction tank is used for locally modifying the sensitive layer, so that the reaction between the sensitive layer and the target molecule occurs in the mass sensitive area of the beam, and a sample to be detected can cause a peak value of deflection or frequency change when flowing through the mass sensitive area of the beam, and meanwhile, the method reduces the influence of large-area adsorption on the elastic constant of the beam, and can effectively improve the detection precision of the hollow micro-nano composite beam sensor.
6. The design method of the hollow micro-nano composite beam for biochemical molecule detection according to claim 1, wherein the hollow micro-nano composite beam structure can adopt an array form, different sensitive layers are modified in reaction tanks of different beams, so that simultaneous detection of multiple objects to be detected can be realized, manufacturing cost is saved to a certain extent, after an experiment is performed, cleaning liquid is injected through a liquid inlet, and cleaning waste liquid is discharged through a liquid outlet, so that the beams can be cleaned simply and without pollution.
7. The method of claim 1, wherein the beam structure includes but is not limited to a rectangular micro-cantilever, a T-shaped micro-cantilever, a circular micro-cantilever, a triangular micro-cantilever, a U-shaped micro-cantilever, and a double-ended clamped beam.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210934979.4A CN115178313A (en) | 2022-08-05 | 2022-08-05 | Design method of hollow micro-nano composite beam for biochemical molecule detection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210934979.4A CN115178313A (en) | 2022-08-05 | 2022-08-05 | Design method of hollow micro-nano composite beam for biochemical molecule detection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115178313A true CN115178313A (en) | 2022-10-14 |
Family
ID=83521773
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210934979.4A Pending CN115178313A (en) | 2022-08-05 | 2022-08-05 | Design method of hollow micro-nano composite beam for biochemical molecule detection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115178313A (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003022731A1 (en) * | 2001-09-07 | 2003-03-20 | Danmarks Tekniske Universitet | Flexible structure with integrated sensor/actuator |
| CN101492150A (en) * | 2009-02-20 | 2009-07-29 | 中国科学院上海微系统与信息技术研究所 | Micro-machine overhang beam simultaneously implementing driving and self-cleaning with single integrated resister |
| CN101713777A (en) * | 2009-11-06 | 2010-05-26 | 天津大学 | Preparation method of reusable micro-cantilever type immunosensor |
| CN102735564A (en) * | 2012-07-13 | 2012-10-17 | 中国科学院半导体研究所 | High-sensitive biochemical sensor based on resonance oscillation type micro cantilever beam structure |
| CN105514258A (en) * | 2015-12-10 | 2016-04-20 | 上海集成电路研发中心有限公司 | Piezoelectric cantilever beam sensor structure and manufacturing method thereof |
| CN108592965A (en) * | 2018-04-20 | 2018-09-28 | 北京大学 | Flexible piezoresistance type microcantilever beam sensor and preparation method thereof |
| CN109879238A (en) * | 2019-01-15 | 2019-06-14 | 江苏大学 | Micro-cantilever device, processing method and a kind of detection method of embedded channel-type |
| CN109974789A (en) * | 2019-04-25 | 2019-07-05 | 天津工业大学 | A kind of high integration mini optical fibre seawater thermohaline depth sensor based on MEMS technology and membrane material |
-
2022
- 2022-08-05 CN CN202210934979.4A patent/CN115178313A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003022731A1 (en) * | 2001-09-07 | 2003-03-20 | Danmarks Tekniske Universitet | Flexible structure with integrated sensor/actuator |
| CN101492150A (en) * | 2009-02-20 | 2009-07-29 | 中国科学院上海微系统与信息技术研究所 | Micro-machine overhang beam simultaneously implementing driving and self-cleaning with single integrated resister |
| CN101713777A (en) * | 2009-11-06 | 2010-05-26 | 天津大学 | Preparation method of reusable micro-cantilever type immunosensor |
| CN102735564A (en) * | 2012-07-13 | 2012-10-17 | 中国科学院半导体研究所 | High-sensitive biochemical sensor based on resonance oscillation type micro cantilever beam structure |
| CN105514258A (en) * | 2015-12-10 | 2016-04-20 | 上海集成电路研发中心有限公司 | Piezoelectric cantilever beam sensor structure and manufacturing method thereof |
| CN108592965A (en) * | 2018-04-20 | 2018-09-28 | 北京大学 | Flexible piezoresistance type microcantilever beam sensor and preparation method thereof |
| CN109879238A (en) * | 2019-01-15 | 2019-06-14 | 江苏大学 | Micro-cantilever device, processing method and a kind of detection method of embedded channel-type |
| CN109974789A (en) * | 2019-04-25 | 2019-07-05 | 天津工业大学 | A kind of high integration mini optical fibre seawater thermohaline depth sensor based on MEMS technology and membrane material |
Non-Patent Citations (2)
| Title |
|---|
| 刘洁瑜等: "《导弹惯性导航技术》", 29 February 2016, 国防工业出版社, pages: 111 * |
| 李岩等: "《精密测量技术》", 30 September 2001, 中国计量出版社, pages: 110 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ricciardi et al. | Integration of microfluidic and cantilever technology for biosensing application in liquid environment | |
| US6575020B1 (en) | Transducer for microfluid handling system | |
| EP1207958B1 (en) | Sensor for microfluid handling system | |
| KR100613398B1 (en) | Element detecting system using cantilever, method for fabrication of the same system and method for detecting micro element using the same system | |
| US7282329B2 (en) | Suspended microchannel detectors | |
| Sang et al. | Surface stress-based biosensors | |
| US7966898B2 (en) | Polymer NEMS for cell physiology and microfabricated cell positioning system for micro-biocalorimeter | |
| US20080011058A1 (en) | Piezoresistive cantilever based nanoflow and viscosity sensor for microchannels | |
| US20040038426A1 (en) | Measurement of concentrations and binding energetics | |
| Sang et al. | Review on the design art of biosensors | |
| Pinto et al. | Label-free biosensing of DNA in microfluidics using amorphous silicon capacitive micro-cantilevers | |
| Muñoz-Galán et al. | Beyond biology: alternative uses of cantilever-based technologies | |
| CN115178313A (en) | Design method of hollow micro-nano composite beam for biochemical molecule detection | |
| Baozheng et al. | FABRICATION OF HOLLOW COMPOSITE STRUCTURE MICROFLUIDIC DOUBLE-END CLAMPED BEAM. | |
| Gopinath et al. | Design and simulation of high sensitive paddle microcantilever sensor for biosensing | |
| Rahimpour et al. | Design and manufacturing of electromechanical chip for rapid measurement of IgG1 antibody in cell-culture supernatant | |
| US20240053290A1 (en) | Biosensors | |
| Xu et al. | Real-time operation of microcantilever-based in-plane resonators partially immersed in a microfluidic sampler | |
| Wang et al. | Integrated of PDMS microfluidic channel with cantilever based bio-sensor | |
| Andalib | Investigation of the role of nanochannels on dynamics of anodic aluminum oxide (AAO) microcantilevers in different gas environments | |
| Kato et al. | Reusable high-frequency electrodeless QCM biosensor with a bare quartz resonator embedded in a silicon microchannel | |
| WANG et al. | FABRICATION OF HOLLOW COMPOSITE STRUCTURE MICROFLUIDIC DOUBLE-END CLAMPED BEAM | |
| Stehrer et al. | High Frequency QCM Flow Cell with Enhanced Accuracy for Liquid and Biochemical Sensing | |
| Töral | Development of a high yield fabrication process for MEMS based resonant mass sensors for cell detection applications | |
| JP2005049145A (en) | Mechanochemical sensor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |