CN107462704A - A kind of biology sensor and preparation method thereof, concentration of target molecules detection method - Google Patents
A kind of biology sensor and preparation method thereof, concentration of target molecules detection method Download PDFInfo
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- CN107462704A CN107462704A CN201710860617.4A CN201710860617A CN107462704A CN 107462704 A CN107462704 A CN 107462704A CN 201710860617 A CN201710860617 A CN 201710860617A CN 107462704 A CN107462704 A CN 107462704A
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- 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
- G01N33/531—Production of immunochemical test materials
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- 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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Abstract
The invention discloses a kind of biology sensor and preparation method thereof, concentration of target molecules detection method.The preparation method of biology sensor comprises the following steps：S1, the one or more in Streptavidin, carboxyl, amino, sulfydryl are modified onto magnetic bead, by the aptamer of biotin modification to target molecule to be detected；S2, the aptamer and the magnetic bead are added in reaction solution, the aptamer is coupled on the moiety site of the magnetic bead；The reaction solution is salt buffer of the concentration in more than 100mM；S3, it be able to will be coupled to the DNA sequence dna of the aptamer complementary pairing on noble metal nano particles；S4, the obtained noble metal nano particles of the obtained magnetic beads of step S2 and step S3 are placed in 5~60min of reaction in hybridization solution, by base pair complementarity, form the biology sensor being made up of magnetic bead, aptamer, noble metal nano particles.The achievable Concentration Testing, and cost is low in high sensitivity of the present invention, efficiency high.
Description
【Technical field】
It is dense more particularly to a kind of biology sensor and preparation method thereof, target molecule the present invention relates to Measurement for Biotechnique
Spend detection method.
【Background technology】
Biomarker is a kind of indicator of the biological condition of disease, and it can be protein, DNA or RNA piece
Section, there is specificity, therefore can be as the mark of targeting disease.Particularly cancer biomarkers thing, it is the sign of cancer.
By detecting them, cancer can be diagnosed.With the development of biotechnology, the biomarkers of many cancers by
It was found that.By the detection to these biomarkers, disease can be diagnosed and treated in the expected time.Wherein albumen
The significant changes of matter can reveal that physiology and pathologic process of the organism as a kind of biomarker, indicate the biology of disease
State.These protein are in the basic research of life science, medical diagnosis on disease, drug research, health analysis and bio-safety
Monitor significant.Protein identification is a kind of wide variety of skill based on antigentic specificity and immune response antibody
Art.But also there are some shortcomings, for example, the time spends more, cost height, immunogenicity, the chemical modification of caused antibody may
Activity is caused to reduce or even inactivate, application of the limitation antibody antigen in protein analysis.Therefore, more convenient, Gao Ling is carried out
The protein identification research of quick high specific is significant to biosystem.
The disclosure of background above technology contents is only used for inventive concept and the technical scheme that auxiliary understands the present invention, and it is not
The prior art of present patent application is necessarily belonged to, shows the applying date of the above in present patent application in no tangible proof
In the case of disclosed, above-mentioned background technology should not be taken to evaluate the novelty and creativeness of the application.
【The content of the invention】
The technical problems to be solved by the invention are：Above-mentioned the deficiencies in the prior art are made up, propose a kind of biology sensor
And preparation method thereof, concentration of target molecules detection method, can be achieved Concentration Testing, and cost is low in high sensitivity, efficiency high.
The technical problem of the present invention is solved by following technical scheme：
A kind of preparation method of biology sensor, comprises the following steps：S1, by Streptavidin, carboxyl, amino, sulfydryl
In one or more kinds of modifications on magnetic bead, by the aptamer of biotin modification to target molecule to be detected；S2,
The aptamer and the magnetic bead are added in reaction solution, the aptamer is coupled to the moiety site of the magnetic bead
On；The reaction solution is salt buffer of the concentration in more than 100mM；S3, by can be with the DNA of the aptamer complementary pairing
Coupling sequence is on noble metal nano particles；S4, the noble metal nano particles that the obtained magnetic beads of step S2 and step S3 are obtained
5~60min of reaction in hybridization solution is placed in, by base pair complementarity, is formed by magnetic bead, aptamer, noble metal nano grain
The biology sensor that son is formed.
The biology sensor of the present invention, is repaiied by the one or more in Streptavidin or carboxyl, amino, sulfydryl
Adorn magnetic bead, by biotin modification aptamer so that aptamer can by Streptavidin (or carboxyl,
Amino, sulfydryl) combination between biotin and be coupled on magnetic bead.It is coupled to by the DNA sequence dna that complementary pairing can be achieved
On noble metal nano particles, so as to realize that follow-up noble metal nano particles coupling is connected on aptamer, magnetic is finally made
Pearl coupling nucleic acid aptamers, upper noble metal nano particles are connected after aptamer base pairing, obtain that there is rock-steady structure
Biology sensor.The biology sensor can play aptamer can directly chemical synthesis, target molecule have a very wide distribution, energy
The advantages of with target molecule specific binding and high affinity, the strong scattering characteristic of noble metal nano particles can be also played, so as to
For high-contrast dark-field imaging, and then realize highly sensitive detection.
In preferable technical scheme, also wrapped after the nucleic acid aptamer sequence is coupled on the magnetic bead in step S2
Include：Free biotin is added in the reaction solution, the biotin is coupled on the other part site of the magnetic bead；
After Magneto separate washing, then sealer is connected on the magnetic bead and closed.
In the preferred scheme, Seal treatment is carried out to the spare bits point on magnetic bead by biotin and sealer, so as to have
Beneficial to the non-specific adsorption for reducing the reaction target in detection process, Counts amount is reduced, improves detection efficiency.
Further, the sealer is the serum of bovine serum albumin, skimmed milk power or no cross reaction.
Further, in step S2, the salt buffer is Tris salt buffer.Specifically, Tris salt buffer
It may include 10mM Tris-HCl (pH 7.5), 1mM EDTA and 2M NaCl.
Further, in step S3, the noble metal nano particles are gold nanoshell particles, gold nano-rod particles, gold/silver
Composite nanometer particle, gold nano star particle, gold nano cubic granules, gold nano bipyramid particle.
Further, in step S4, the hybridization solution includes PBS, NaCl solution and SDS.
Further, the PBS cushioning liquid that the hybridization solution includes 10mM, pH value is 7.4,0.3m NaCl, 0.01%
SDS。
A kind of biology sensor according to made from preparation method as described above.
The technical problem of the present invention is solved by technical scheme further below：
A kind of concentration of target molecules detection method, comprises the following steps：A1, according to the system described in any one of claim 1~6
Biology sensor is made in Preparation Method；A2, divided in detection with the target that the biology sensor and concentration to be determined are added in reaction solution
Sub- solution, fully reaction so that the noble metal nano particles in the biology sensor dissociate into reaction solution；A3, lead to
Cross and surface modification is carried out to slide comprising one or more kinds of solution of silane in amino, carboxyl, sulfydryl, hydroxyl, make institute
The surface for stating slide forms one layer of self-assembled film；A4, by magnetic separation technique, the supernatant in aspiration step A2 in reaction solution
Liquid, it is placed on step A3 slide and sample is made, the noble metal nano particles in sample is counted using dark field microscope
Number；A5, it is molten according to the number of the noble metal nano particles and target molecule under step A4 counting and dark field microscope analysis
Calibration curve between liquid concentration, the concentration of current molecule solution is calculated
In the concentration of target molecules detection method of the present invention, detected using foregoing obtained biology sensor, during detection
After adding target molecule, in the presence of having target molecule, aptamer occurs adaptability and folds to form three-dimensional structure, with target
Molecule in close combines, and causes the double-strand base pairing of aptamer and noble metal nano particles to be destroyed, so that noble metal
Nano-particle dissociates into reaction solution.Dark field analysis counting is carried out subsequently through to noble metal nano particles, you can is calculated
The concentration of the target molecule of addition.The antigen and antibody specific being different from traditional detection method combines, and utilizes aptamer
High specific and high-affinity, specific detection can be realized to the bio-target molecule of protide.And utilize the excellent of gold nano grain
The high contrastive feature of different characteristic and details in a play not acted out on stage, but told through dialogues micro-imaging technique, realizes monomolecular micro-imaging, really realizes the Gao Ling of detection
Quick characteristic.
Further, in step A3, the solution of silane is 3- aminopropyl triethoxysilane solution.
The beneficial effect that the present invention is compared with the prior art is：
The preparation method of the biology sensor of the present invention, realizes aptamer and is coupled on magnetic bead, noble metal nano
Particle is connected on aptamer by DNA pairings, and then is formed by magnetic bead, nucleic acid aptamer sequence, noble metal nano grain
The biology sensor that son is formed.In detection process, it is only necessary to add target molecule i.e. can be achieved noble metal nano particles release and then
High-sensitivity detection, whole detection process is simple and quick, and cost is low.And pass through aptamer and DNA in biology sensor
Sequence realizes connection, and without individually designed probe sequence, and aptamer is readily synthesized, and chemical modification is simple, and without immune
Originality, relative to scheme of the antigen-antibody as probe was used in the past, the cost of biology sensor can be also significantly reduced, improves life
The stability of thing sensor.
【Brief description of the drawings】
Fig. 1 a are the principle schematics of the concentration of target molecules detection method of the specific embodiment of the invention；
Fig. 1 b are the process schematics of the concentration of target molecules detection method of the specific embodiment of the invention；
Fig. 2 is the scanning electron microscope (SEM) photograph and dark field microscope photo of the gold nano grain of the specific embodiment of the invention；
Fig. 3 is the scanning electron microscope (SEM) photograph that front and rear magnetic bead is reacted in the specific embodiment of the invention；
Fig. 4 is the details in a play not acted out on stage, but told through dialogues photo correspondingly obtained under various concentrations when being calibrated in the specific embodiment of the invention；
Fig. 5 is the curve synoptic diagram calibrated out in the specific embodiment of the invention；
Fig. 6 be in the specific embodiment of the invention under various different targets corresponding absorbance schematic diagram.
【Embodiment】
Idea of the invention is that：Aptamer (Apatamer) is one section of single-chain nucleic acid with specific recognition function
Molecule, it can be synthesized in vitro by the Fas lignand system evolution technology of index concentration.Found by studying, in target (namely target
Molecule) in the presence of, aptamers can occur adaptability and fold to form three-dimensional structure, for example, the serobilas of G- tetra-, hair clip, bulge loop,
False knot.Combined closely by the complementary pairing of base, shape complementation, Van der Waals force, electrostatic interaction and hydrogen bond etc. with target.Target
Corresponded with its aptamer, such as target A can allow its corresponding aptamers B to fold, and form three-dimensional structure；Target
A1 can allow corresponding aptamers B1 to fold, and form three-dimensional structure.In addition, with antibody on the contrary, aptamer is easy to close
Into chemical modification is simple, and non-immunogenicity.And the most important feature of aptamers is extensive target molecule distribution, including with
The protein of aptamer, virus, cell etc..Therefore, the adaptability for causing aptamer based on target folds, and considering will
Aptamer is used as the good identification molecule in target concentration detection.
Noble metal nano particles, such as gold nano grain (AuNPs), gold nano-rod particles, gold/silver-colored composite nanometer particle,
The research of gold nano star particle, gold nano cubic granules, gold nano bipyramid particle etc. is always focus, noble metal nano particles
Good biocompatibility, specific surface area is big, is easy to modify, and has good optical characteristics.And its synthetic method is ripe, change phase
Condition is answered, different size, the noble metal nano particles of different shape can be synthesized, therefore be widely used in multiple fields.Your gold utilized
The method that category nano-particle is detected to biomolecule mainly has colorimetric method, fluorescence method, chemoluminescence method, electrochemistry, surface
Strengthen Raman etc..But wherein its detection sensitivity of colorimetric method, fluorescence method, chemoluminescence method is low, be not suitable for highly sensitive cancer
Target detection.And the methods of electrochemistry, surface-enhanced Raman, it is cumbersome, spend the time longer, it is difficult to actually should in clinic
With.Noble metal nano particles are due to its preferable biocompatibility and stronger scattering properties, available for the dark of high-contrast
Field imaging, and then realize the research that unimolecule directly counts.
To sum up, the present invention is proposed using the magnetic bead for having modified aptamer as matrix, is formed with noble metal nano particles
The scheme of biology sensor, the magnetic bead of aptamer, gold nano grain and bioid is self-assembly of biology sensor.
When the biology sensor is used for concentration of target molecules detection, by the use of magnetic bead as the basis of Magneto separate, biology will be departed from after reaction and passed
The noble metal nano particles of sensor isolate reaction system.Then picture is gathered by dark field microscope and imaging sensor, and
The picture of collection is handled using picture Processing Technique and counts the number of noble metal nano particles, and then draws target molecule
Concentration, realize the high-sensitivity detection to monomolecular bio-target molecule concentration.
With reference to embodiment and compare accompanying drawing the present invention is described in further details.
Detected in present embodiment by target molecule of fibrin ferment, Cleaning Principle schematic diagram as shown in Figure 1a, is examined
Survey process schematic as shown in Figure 1 b.
Step 1：Design two sections of sequences：
First paragraph is the sequence of aptamer, and it can determine that to obtain according to target molecule (i.e. fibrin ferment) to be detected：
5 '-biotin-TTTTTTTTTTTTTTTTTTTTGGTTGGTGTGGTTGG-3 ', it is repaiied using biotin
Decorations, then it is coupled on the magnetic bead of Streptavidin modification.Reaction solution is 10mM Tris-HCl (pH 7.5), 1mM
EDTA and 2M NaCl mixed liquor.Under remaining embodiment, it can also pass through the one or more in carboxyl, amino, sulfydryl
To modify magnetic bead, after these base group modification magnetic beads, can equally be combined with biotin, so as to realize between aptamer and magnetic bead
Coupling.
Second segment is the DNA sequence dna with aptamer complementary pairing, and it is obtained according to first paragraph sequences Design：
5 '-SH-TTTTTTTTTTTTTTTTTTTTCCAAC-3 ', it is coupled on gold nano grain and forms nanometer spy
Pin.
In present embodiment, in order to reduce the non-specific adsorption on magnetic bead, free biotin and ox blood are used
Albumin is closed to its redundant bit point.Specific steps include：The reaction of magnetic bead is coupled in reaction solution amplifying nucleic acid aptamers
And then free biotin is added, 15min is reacted, free biotin is coupled to the other part site of the magnetic bead
On.Magneto separate washs and then added reaction solution, adds BSA and closing 1h is carried out under the conditions of 4 DEG C.
Fig. 2 is the scanning electron microscope (SEM) photograph (left side) and dark field microscope photo of the gold nano grain used in present embodiment
(right side).
Step 2：The coupling that step 1 is produced has the magnetic bead of aptamer and coupling to have the gold nano of DNA sequence dna
Particle be mixed in hybridization solution (10mM PBS7.4,0.3mM NaCl, 0.01%SDS (and Sodium dodecyl sulfate, ten
Sodium dialkyl sulfate)) in, after reacting 30min, biology sensor is obtained, after reaction terminates, magnetic point is carried out by externally-applied magnetic field
From centrifuge washing, isolating the biology sensor formed by aptamer, magnetic bead, noble metal nano particles.
Fig. 3 is the scanning electron microscope (SEM) photograph of the front and rear magnetic bead of reaction, and wherein a is the magnetic bead for not connecting gold nano grain, and b is magnetic
The scanning electron microscope (SEM) photograph of the biology sensor formed after the upper gold nano grain of pearl connection.
Step 3：Curve is calibrated：
In reaction solution (20mM Tris-HCl, pH7.4,140mM NaCl, the 1mM MgCl of detection2, 5mM's
KCl, 1mM CaCl2, 1mg/mL BSA) in, the fibrin ferment for adding various concentrations (known to concentration) carries out calibration detection, reacts
Time is 30min.Magneto separate afterwards, 3 μ L supernatant is taken in the sheet glass with 3- aminopropyl triethoxysilanes with liquid-transfering gun,
The cover glass washed with Piranha washing lotion is pressed in forms detection sample above, carries out observation with dark field microscope and takes pictures.It is different dense
The lower corresponding obtained details in a play not acted out on stage, but told through dialogues photo of degree is made as shown in figure 4, wherein, control groups illustrate that picture when being added without fibrin ferment
For control group.
Data handling procedure：The picture of details in a play not acted out on stage, but told through dialogues is acquired by imaging sensor, recycles matlab programs to carry out
Picture processing is simultaneously counted, and is made curve according to obtained data and the concentration known of bio-target molecule (fibrin ferment), is obtained Y
=6.08506*X+115.199, R-Square=0.98593.As shown in figure 5, it is the curve calibrated out, it can be seen that experiment
As a result linear good, data are reliable.The inspection of the detection method of present embodiment can be calculated according to LOD=3 × Sb/S
Survey lower limit is 2.54fM.
Fig. 6 illustrates the absorbance at the top of corresponding gold nano grain under various different targets, fibrin ferment in figure
(100nM), cytochromes (1 μM), lysozyme (1 μM), immunoglobulin (1 μM), bovine serum albumin (1 μM), trypsase (1 μ
M), the absorbance under blank group is different, significant difference, so as to also demonstrate the Gao Te of biology sensor made from step 2
The opposite sex, show high application value.
Step 4：It is actually detected：
In reaction solution (20mM Tris-HCl, pH7.4,140mM NaCl, the 1mM MgCl of detection2, 5mM's
KCl, 1mM CaCl2, 1mg/mL BSA) in, the fibrin ferment for adding concentration to be determined carries out actually detected, fully reaction.It
Magneto separate afterwards, 3 μ L supernatant is taken to be washed in the sheet glass with 3- aminopropyl triethoxysilanes with Piranha washing lotion with liquid-transfering gun
The cover glass crossed is pressed in forms detection sample above, carries out observation with dark field microscope and takes pictures.By imaging sensor to details in a play not acted out on stage, but told through dialogues
Picture be acquired, recycle matlab programs to carry out picture processing and simultaneously counted, count counting number, substitute into calibration
In curve, conversion obtains the concentration of current fibrin ferment to be determined.
The detection to concentration of thrombin is realized in present embodiment, its Monitoring lower-cut can have with as little as 2.54fM
There is high sensitivity.Detection process is easy, efficiency high, and cost is low.And the specificity of the detection process is also high, is widely portable to it
The Concentration Testing of its target.
Above content is to combine specific preferred embodiment further description made for the present invention, it is impossible to is assert
The specific implementation of the present invention is confined to these explanations.For general technical staff of the technical field of the invention,
Some replacements or obvious modification are made on the premise of not departing from present inventive concept, and performance or purposes are identical, should all be considered as
Belong to protection scope of the present invention.
Sequence table
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<120>A kind of biology sensor and preparation method thereof, concentration of target molecules detection method
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Claims (10)
- A kind of 1. preparation method of biology sensor, it is characterised in that：Comprise the following steps：S1, by Streptavidin, carboxyl, One or more in amino, sulfydryl are modified onto magnetic bead, and the nucleic acid of biotin modification to target molecule to be detected is adapted to On body；S2, the aptamer and the magnetic bead are added in reaction solution, the aptamer is coupled to the magnetic bead Moiety site on；The reaction solution is salt buffer of the concentration in more than 100mM；S3, can be mutual with the aptamer Recruit to DNA sequence dna be coupled on noble metal nano particles；S4, your gold that the obtained magnetic beads of step S2 and step S3 are obtained Category nano-particle is placed in hybridization solution 5~60min of reaction, by base pair complementarity, is formed by magnetic bead, aptamer, expensive The biology sensor that metal nanoparticle is formed.
- 2. the preparation method of biology sensor according to claim 1, it is characterised in that：The nucleic acid is fitted in step S2 Ligand sequence also includes after being coupled on the magnetic bead：Free biotin is added in the reaction solution, by the biotin It is coupled on the other part site of the magnetic bead；After Magneto separate washing, then sealer is connected on the magnetic bead and sealed Close.
- 3. the preparation method of biology sensor according to claim 2, it is characterised in that：The sealer is cow's serum egg In vain, the serum of skimmed milk power or no cross reaction.
- 4. the preparation method of biology sensor according to claim 1, it is characterised in that：In step S2, the salt buffer Liquid is Tris salt buffer.
- 5. the preparation method of biology sensor according to claim 1, it is characterised in that：In step S3, the noble metal Nano-particle is gold nanoshell particles, gold nano-rod particles, gold/silver-colored composite nanometer particle, gold nano star particle, gold nano cube Body particle, gold nano bipyramid particle.
- 6. the preparation method of biology sensor according to claim 1, it is characterised in that：In step S4, the hybridization solution Including PBS, NaCl solution and SDS.
- 7. the preparation method of biology sensor according to claim 6, it is characterised in that：The hybridization solution include 10mM, PH value be 7.4 PBS cushioning liquid, 0.3m NaCl, 0.01%SDS.
- A kind of 8. biology sensor made from preparation method according to any one of claim 1~7.
- A kind of 9. concentration of target molecules detection method, it is characterised in that：Comprise the following steps：A1, it is any according to claim 1~7 Biology sensor is made in preparation method described in；A2, in detection with adding the biology sensor and to be determined in reaction solution The molecule solution of concentration, fully reaction so that the noble metal nano particles in the biology sensor dissociate to reaction In liquid；A3, by carrying out surface to slide comprising one or more kinds of solution of silane in amino, carboxyl, sulfydryl, hydroxyl Modification, the surface of the slide is set to form one layer of self-assembled film；A4, by magnetic separation technique, reaction solution in aspiration step A2 In supernatant, be placed on step A3 slide and sample be made, using dark field microscope to the noble metal nano grain in sample Son is counted；A5, according to step A4 counting and dark field microscope analysis under the noble metal nano particles number with Calibration curve between molecule solution concentration, the concentration of current molecule solution is calculated.
- 10. concentration of target molecules detection method according to claim 9, it is characterised in that：In step A3, the solution of silane For 3- aminopropyl triethoxysilane solution.
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Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101713779A (en) * | 2009-12-22 | 2010-05-26 | 陕西北美基因股份有限公司 | Method for performing immunological test on biomolecules by avidin/streptavidin magnetic composite particles |
| CN102796824A (en) * | 2012-09-03 | 2012-11-28 | 南京大学 | Detection reagent and detection kit of thrombin and application |
| CN104034712A (en) * | 2014-06-30 | 2014-09-10 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | Kit for detecting thrombin with adapters and suspension chip |
| CN105132533A (en) * | 2015-07-24 | 2015-12-09 | 清华大学深圳研究生院 | Target molecule concentration detection method |
| CN105319190A (en) * | 2014-07-31 | 2016-02-10 | 陶建臣 | Novel detection method of chloramphenicol based on up-conversion fluorescence labeling and magnetic separation technology |
| CN106198503A (en) * | 2016-07-05 | 2016-12-07 | 汕头大学 | A kind of electrochemiluminescence sandwich biosensor and preparation and application |
| CN106290831A (en) * | 2016-08-02 | 2017-01-04 | 中国农业科学院农业质量标准与检测技术研究所 | A kind of competition law test strip based on antigen aptamers and application thereof |
| CN106525814A (en) * | 2016-11-07 | 2017-03-22 | 华南师范大学 | PSA detection method based on magnetic core-gold satellite assembly body |
| CN106568975A (en) * | 2016-11-03 | 2017-04-19 | 清华大学深圳研究生院 | Concentration detection method of plurality of target molecules |
| CN106770163A (en) * | 2016-12-19 | 2017-05-31 | 中国科学院长春光学精密机械与物理研究所 | A kind of detection method of fibrin ferment |
| CN106932376A (en) * | 2017-03-02 | 2017-07-07 | 江苏大学 | A kind of mycotoxin super sensitivity detection method of the gold silver core-shell nanometer rod based on DTNB marks |
-
2017
- 2017-09-21 CN CN201710860617.4A patent/CN107462704A/en active Pending
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101713779A (en) * | 2009-12-22 | 2010-05-26 | 陕西北美基因股份有限公司 | Method for performing immunological test on biomolecules by avidin/streptavidin magnetic composite particles |
| CN102796824A (en) * | 2012-09-03 | 2012-11-28 | 南京大学 | Detection reagent and detection kit of thrombin and application |
| CN104034712A (en) * | 2014-06-30 | 2014-09-10 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | Kit for detecting thrombin with adapters and suspension chip |
| CN105319190A (en) * | 2014-07-31 | 2016-02-10 | 陶建臣 | Novel detection method of chloramphenicol based on up-conversion fluorescence labeling and magnetic separation technology |
| CN105132533A (en) * | 2015-07-24 | 2015-12-09 | 清华大学深圳研究生院 | Target molecule concentration detection method |
| CN106198503A (en) * | 2016-07-05 | 2016-12-07 | 汕头大学 | A kind of electrochemiluminescence sandwich biosensor and preparation and application |
| CN106290831A (en) * | 2016-08-02 | 2017-01-04 | 中国农业科学院农业质量标准与检测技术研究所 | A kind of competition law test strip based on antigen aptamers and application thereof |
| CN106568975A (en) * | 2016-11-03 | 2017-04-19 | 清华大学深圳研究生院 | Concentration detection method of plurality of target molecules |
| CN106525814A (en) * | 2016-11-07 | 2017-03-22 | 华南师范大学 | PSA detection method based on magnetic core-gold satellite assembly body |
| CN106770163A (en) * | 2016-12-19 | 2017-05-31 | 中国科学院长春光学精密机械与物理研究所 | A kind of detection method of fibrin ferment |
| CN106932376A (en) * | 2017-03-02 | 2017-07-07 | 江苏大学 | A kind of mycotoxin super sensitivity detection method of the gold silver core-shell nanometer rod based on DTNB marks |
Cited By (15)
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| CN108841923A (en) * | 2018-06-07 | 2018-11-20 | 南京邮电大学 | A kind of quantum dot based on DSN enzyme-magnetic bead miRNA sensor and preparation method thereof and detection method |
| CN109593764A (en) * | 2018-12-21 | 2019-04-09 | 宁波大学 | Saxitoxin quickly detects aptamer biosensor and preparation method thereof |
| CN109593764B (en) * | 2018-12-21 | 2021-07-27 | 宁波大学 | Aptamer biosensor for rapidly detecting saxitoxin and preparation method thereof |
| CN109782000A (en) * | 2019-03-06 | 2019-05-21 | 清华大学深圳研究生院 | A kind of concentration detection method of c reactive protein |
| CN112326957A (en) * | 2019-07-16 | 2021-02-05 | 四川大学 | Ratio type DNA molecular machine for biological analysis |
| CN112113948A (en) * | 2020-08-05 | 2020-12-22 | 武汉市农业科学院 | Rapid detection method for pathogenic microorganisms |
| CN112014369A (en) * | 2020-08-25 | 2020-12-01 | 上海市皮肤病医院 | System and method for quickly detecting analyte by using ultrasensitive digital chromatography |
| CN112014369B (en) * | 2020-08-25 | 2024-02-09 | 上海市皮肤病医院 | System and method for ultrasensitive digital chromatography rapid detection of analytes |
| CN113075191A (en) * | 2021-03-17 | 2021-07-06 | 南通大学 | High-sensitivity miRNA detection method based on Raman spectroscopy |
| CN113447467A (en) * | 2021-06-04 | 2021-09-28 | 厦门大学 | Method for detecting SARS-CoV-2 antigen of new coronavirus |
| CN113447467B (en) * | 2021-06-04 | 2022-05-13 | 厦门大学 | Method for detecting SARS-CoV-2 antigen of new coronavirus |
| CN113933364A (en) * | 2021-09-03 | 2022-01-14 | 中国科学院上海微系统与信息技术研究所 | Target concentration detection method based on silicon nanowire field effect biochemical sensor |
| CN115508329A (en) * | 2022-08-12 | 2022-12-23 | 厦门大学 | Method for detecting novel coronavirus N protein based on surface enhanced Raman spectroscopy |
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