CN1534295A - Preparation method of protein chip - Google Patents
Preparation method of protein chip Download PDFInfo
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- CN1534295A CN1534295A CNA03116076XA CN03116076A CN1534295A CN 1534295 A CN1534295 A CN 1534295A CN A03116076X A CNA03116076X A CN A03116076XA CN 03116076 A CN03116076 A CN 03116076A CN 1534295 A CN1534295 A CN 1534295A
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- solid phase
- avidin
- phase carrier
- biotin
- protein
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- 238000002360 preparation method Methods 0.000 title claims description 10
- 108090000623 proteins and genes Proteins 0.000 title abstract description 19
- 102000004169 proteins and genes Human genes 0.000 title abstract description 18
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims abstract description 100
- 229960002685 biotin Drugs 0.000 claims abstract description 59
- 239000011616 biotin Substances 0.000 claims abstract description 59
- 108090001008 Avidin Proteins 0.000 claims abstract description 58
- 235000020958 biotin Nutrition 0.000 claims abstract description 50
- 239000000758 substrate Substances 0.000 claims abstract description 12
- 239000007790 solid phase Substances 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 11
- 238000013016 damping Methods 0.000 claims description 9
- 239000012530 fluid Substances 0.000 claims description 9
- 108010090804 Streptavidin Proteins 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 239000011521 glass Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 239000000020 Nitrocellulose Substances 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 229920001220 nitrocellulos Polymers 0.000 claims description 5
- 239000002985 plastic film Substances 0.000 claims description 5
- 239000012528 membrane Substances 0.000 claims description 4
- 238000002791 soaking Methods 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- 238000002372 labelling Methods 0.000 claims description 3
- 238000009792 diffusion process Methods 0.000 abstract description 6
- 230000035945 sensitivity Effects 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract 2
- 239000000126 substance Substances 0.000 abstract 2
- 238000005070 sampling Methods 0.000 description 11
- 239000000427 antigen Substances 0.000 description 10
- 102000036639 antigens Human genes 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 238000007789 sealing Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000002131 composite material Substances 0.000 description 6
- FJWGYAHXMCUOOM-QHOUIDNNSA-N [(2s,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6s)-4,5-dinitrooxy-2-(nitrooxymethyl)-6-[(2r,3r,4s,5r,6s)-4,5,6-trinitrooxy-2-(nitrooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-3,5-dinitrooxy-6-(nitrooxymethyl)oxan-4-yl] nitrate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O)O[C@H]1[C@@H]([C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@@H](CO[N+]([O-])=O)O1)O[N+]([O-])=O)CO[N+](=O)[O-])[C@@H]1[C@@H](CO[N+]([O-])=O)O[C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O FJWGYAHXMCUOOM-QHOUIDNNSA-N 0.000 description 4
- 208000005176 Hepatitis C Diseases 0.000 description 3
- -1 compound compound Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000002493 microarray Methods 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 244000309466 calf Species 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000000018 DNA microarray Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical group O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
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- 238000011010 flushing procedure Methods 0.000 description 1
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- 230000004927 fusion Effects 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Peptides Or Proteins (AREA)
Abstract
A solid carrier of protein chip is composed of a substrate, a biotin marked enclosing substance layer on said substrate, and an avidin layer on said enclosing substance layer. Its advantages are less diffusion of sample applied point and high sensitivity. A process for preparing the solid carrier of protein chip is also disclosed.
Description
Technical field
The invention belongs to protein-chip or immunoassays field, relate more specifically to a kind of new protein chip carrier and disposal route thereof.
Background technology
Detect for improving flux and detection efficiency, development in recent years a kind of microarray enzyme linked immunosorbent detection technology of having got up is also referred to as protein biochip technology---and what its utilized is that the specificity that antibody combines with antigen is that immune response comes test sample.
The simplified model that protein-chip makes up is: select a kind of solid phase carrier conjugated protein molecule (antigen or antibody) securely, form the microarray of protein like this, i.e. protein-chip.Make up protein microarray on substrate, each point in the array is being represented an independently biochemical reaction, carries out thereby various reactions is integrated on the very little carrier.
In the protein-chip manufacture process, the preparation of solid phase carrier is extremely important with processing.The solid phase carrier that is used to make protein-chip has two big classes: a class is two-dimentional holders such as glass, polystyrene, and a class is three dimensional support such as NC film, PDVF film, each gellike.
General technology flow process with NC film or PDVF film production protein-chip is as follows:
(1) main points are mixed with finite concentration to antigen or antibody on the film with damping fluid,
(2) with high speed robot's point sample instrument protein---antigen or antibody are put on the film,
(3) use damping fluid rinsing film 2-3 time, each 3-6 minute,
(4) with 5% calf serum or took off under the ester milk powder room temperature sealing 1-2 hour,
(5) use damping fluid rinsing film 2-3 time again, each 3-6 minute.
The film class solid phase carrier that is used to make protein-chip belongs to three-dimensional structure, and its advantage is that film is big to the protein adsorption amount of point sample, and enzyme-labelled antigen or antibody amount through being fixed on after the immune response on the film are big, and detection signal is higher relatively.
Be that film is fixing just because film produces the absorption of proteins effect to protein, a little less than the bed knife, can cause coming off through flushing repeatedly yet make its maximum shortcoming of holder with film.With the solid phase carrier of film with protein-chip, the background height that signal produces, and heterogeneity.And protein array spreads in course of reaction easily, and battle array is particularly when density is big, and the signal that easily causes difference is owing to apart from too closely influencing each other.
Therefore, this area presses for new protein-chip solid phase carrier of exploitation and preparation method thereof, and this solid phase carrier can significantly reduce the diffusion of protein spots sampling point and/or improve detection sensitivity.
Summary of the invention
Purpose of the present invention just provides a kind of new protein-chip solid phase carrier and preparation method thereof, and this solid phase carrier can significantly reduce the diffusion of protein spots sampling point and/or improve detection sensitivity.
In a first aspect of the present invention, a kind of solid phase carrier of protein-chip is provided, it comprises:
The solid phase carrier substrate,
Be positioned at the closure layer on the described surface of solid phase carriers, wherein said closure is by biotin labeling; And
Be positioned at the Avidin layer on the closure layer;
Wherein in closure layer and Avidin layer, the quantity of biotin is the 0.15-0.4 of Avidin active unit.
In another preference, described solid phase carrier substrate is selected from down group: glass sheet, plastic sheet, nitrocellulose membrane, PDVF film.
In another preference, the total content of described Avidin-biotin is 5-1000ug/cm
2
In another preference, described Avidin is selected from down group: white of an egg Avidin, Streptavidin, and composition thereof.
In another preference, described biotin is selected from down group: biotin N-maloyl imines ester, long-armed biotin or its potpourri.
In a second aspect of the present invention, a kind of preparation method of protein-chip solid phase carrier is provided, comprise step:
(a) a solid phase carrier substrate is soaked in the biotin labeled closure solution,
(b) solid phase carrier of usefulness damping fluid washing step (a);
(c) solid phase carrier of drying steps (b);
(d) solid phase carrier with step (c) is soaked in the Avidin solution, and wherein to make the quantity of biotin be the 0.15-0.4 of Avidin active unit to the concentration of Avidin,
(e) solid phase carrier of usefulness damping fluid washing step (d);
(f) solid phase carrier of drying steps (e).
In another preference, described solid phase carrier is selected from down group: glass sheet, plastic sheet, nitrocellulose membrane, PDVF film.
In another preference, in the described Avidin solution Avidin concentration be 5-1000ug/ml.
In another preference, described Avidin is selected from down group: white of an egg Avidin, Streptavidin, and composition thereof; And described biotin is selected from down group: biotin N-maloyl imines ester, long-armed biotin or its potpourri.
In another preference, step (a) and (d) soaking conditions be under the room temperature 90-150 minute, or 4 ℃ are spent the night; And drying condition is room temperature airing or freeze drying.In another preference, described Avidin is selected from down group: white of an egg Avidin, Streptavidin, and composition thereof.
Description of drawings
Fig. 1 is the diagrammatic cross-section of solid phase carrier of the present invention.
Embodiment
The inventor is extensive studies through going deep into, and when discovery has biotin labeled closure layer and Avidin layer when the surface combination of the solid phase carrier of protein-chip, not only can significantly reduce the diffusion of protein spots sampling point, and can improve detection sensitivity.Finished the present invention on this basis.
The Avidin layer formation that protein-chip solid phase carrier of the present invention is positioned at the carrier biotin labeled closure layer in top and (c) is positioned at closure layer top by (a) conventional solid phase carrier (being substrate), (b) basically.
Between the closure layer and Avidin layer of protein-chip solid phase carrier of the present invention, formed specific Avidin-biotin composite, this is a kind of compound by a certain proportion of Avidin and biotin be combined into.Usually, the Avidin of 1 molecule forms compound compound fully in conjunction with the biotin of 4 molecules.Compound right and wrong of the present invention are compound compound fully, promptly per 1 molecule Avidin with less than the formed compound of the biotin of 4 molecules.Preferable compound be per 1 molecule Avidin with less than the formed compound of the biotin of 0.6-2 molecule, more preferably be per 1 molecule Avidin and less than the formed compound of the biotin of 0.8-1.5 molecule.
The mode of biotin/avidin ratio is to be benchmark with Avidin active unit in another kind of expression Avidin-biotin composite.Avidin active unit be defined as some Avidins energy in conjunction with the quantity of biotin.In compound of the present invention, the quantity of biotin is generally the 0.15-0.4 of Avidin active unit, preferably is 1/5-1/3.
Can be used for Avidin of the present invention is not particularly limited.Representational example comprises (but being not limited to): white of an egg Avidin, Streptavidin or its potpourri etc.
Can be used for biotin of the present invention is not particularly limited.Representational example comprises (but being not limited to): activation biotin, the plain N-maloyl of biological example imines ester, long-armed biotin, biotin hydrazides or its potpourri etc.
Can be used for closure of the present invention is not particularly limited.Representational example comprises (but being not limited to) calf serum, takes off ester milk powder or its compound.
As used herein, term " protein-chip solid phase carrier " is exactly a substrate material of putting the protein spots sampling point thereon, and common carrier comprises: glass sheet, plastic sheet, cellulose nitrate (NC) film, PDVF film etc. wherein particularly preferably are the NC film.
The present invention also provides the preparation method of protein-chip solid phase carrier.With the NC film is example, and its disposal route comprises the steps:
(1) pre-sealing
With mark the closure of biotin protein-chip solid phase carrier film (substrate) is sealed in advance, thereby on solid phase carrier, form the closure layer.
A kind of preferable methods be with weight concentration be 2%-10% mark the closure of biotin to sealing as protein-chip solid phase carrier film, crossed liquid in 1-2 hour or 4 ℃ under the room temperature.
As for soaking temperature and time, be not particularly limited.Usually, the soak time in Avidin-biotin composite solution is under the room temperature 90-150 minute or longer, or 4 ℃ are spent the night.
The concentration of biotin labeled closure is generally 5-1000ug/ml in the pre-lock solution, is 100ug/ml-500ug/ml preferably, presses the cubage of biotin.
(2) Avidin is handled
In this step, handle the solid phase carrier of pre-sealing with Avidin.The biology that is used on Avidin and the closure have very high affinity, therefore can form one deck Avidin molecular layer again on solid phase carrier.So just formed solid phase carrier of the present invention.As for soaking temperature and time, be not particularly limited.Usually, the soak time in Avidin-biotin composite solution is under the room temperature 90-150 minute or longer, or 4 ℃ are spent the night.
A kind of preferable methods is film to be soaked 10-30 minute the room temperature airing with the Avidin of 0.1mg/ml-1.0mg/ml again after sealing is finished.
For protein-chip solid phase carrier of the present invention, available conventional method, with point sample instrument will be with biotin labeling antigen or antibody put on film, after room temperature airing or the freeze drying, just formed protein-chip.
Avidin concentration is generally 5-1000ug/ml in the Avidin solution, preferably is 100ug/ml-500ug/ml.In addition, the ratio of the biotin volumetric molar concentration in the volumetric molar concentration of the Avidin in the Avidin solution and the closure solution is 1: 0.5-1: 4, and preferably be 1: 1-1: 2.Like this, the biotin proportion is the 1/5-1/3 of Avidin active unit in the Avidin-biotin composite that forms on solid phase carrier of the present invention.Certainly, condition such as soak time is to Avidin in Avidin-biotin composite: the ratio of biotin also can be influential.
By using protein-chip method for making of the present invention, on NC, PDVF film, form one deck and had active continuous albuminous membranae, mark the antigen of biotin or antibody by the imidazolone ring of biotin and the binding site position strong bonded on the Avidin, thereby reach four aspect effects:
1, reduced non-specific adsorption;
2, sealing homogeneous, firm, the minimizing that comes off of film adsorbed proteins in the washing process;
3, the combination on film of the antigen of point sample or antibody is firm, and fully is exposed in the space, has reduced space steric effect;
4, antigen or the diffusion of antibody on film in the course of reaction have been reduced.
According to test, handle the NC film by the present invention after, carry out the protein point sample again, through antigen-antibody reaction, the background values of the final sample signal 10-15% that can descend, corresponding sample minimum detectable activity also can reduce more than 10%, thus detection sensitivity is greatly improved.
In addition, the NC film is through handling, and the diffusion of protein sampling point also reduces to some extent, and sampling point area ratio is 1.5 times before and after the immune response, and the two untreated area ratio is more than 3.2 times.In other words, point of sample area of the present invention only is about 50% of contrast.Therefore, the NC film of handling through Avidin-biotin, after the luminescence-producing reaction in the same hole between the difference phase mutual interference of light signal reduced greatly, also indicating the integrated level that can further improve protein-chip.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, people such as Sambrook for example, molecular cloning: laboratory manual (New York:Cold Spring Harbor Laboratory Press, 1989) condition described in, or the condition of advising according to manufacturer.
Embodiment 1
Below be that example is further set forth the present invention with hepatitis C anti-HCV kind detection of antibodies, but be not limited to scope of the present invention.
(a) preparation of protein-chip solid phase carrier
The aperture 0.4mm water wettability NC film of selecting Whatman company to produce, the PBS of 2-10%, the pH 7.8 that changes with long-armed biotin (BCNHS) takes off the sealing of ester milk powder damping fluid, under the room temperature sealing 1-2 hour or 4 ℃ liquid.The PBS damping fluid washing of PH7.8 3 times, the room temperature airing; Solution of streptavidin with 0.5% was soaked 30 minutes, airing.
(b) preparation of protein-chip
The gene fusion antigen of the long-armed biotin (BCNHS) of hepatitis C being changed with the high speed point sample instrument (comprise Core NS3 NS4 NS5) put on the NC of above-mentioned processing film, the individual sampling point of every array 16 (4 * 4), each sampling point diameter 0.4mm, the room temperature airing.
(c) detect
Respectively the protein-chip of making in order to said method, detect the serum of the hepatitis C positive with the protein-chip of making through usual method, film reaction is the result be compared as follows:
Embodiment 2
Repeat the order-checking of embodiment 1, difference only has been to use variable concentrations Avidin and biotin, different Avidin: the ratio of biotin and different solid phase carriers (seeing table 2 for details).
Table 2
| Solid phase carrier | Biotin quantity is the ratio of Avidin active unit | Avidin concentration (ug/ml) | Reaction back control treatment sampling point area (experimental point sampling point size/control point sampling point size) |
| ??NC | ????1/3 | ????50 | ????0.55 |
| ????100 | ????0.52 | ||
| ????300 | ????0.48 | ||
| ??PDVF | ????1/4 | ????50 | ????0.56 |
| ????100 | ????0.53 | ||
| ????300 | ????0.46 |
Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (10)
1. the solid phase carrier of a protein-chip is characterized in that, it comprises:
The solid phase carrier substrate,
Be positioned at the closure layer on the described surface of solid phase carriers, wherein said closure is by biotin labeling; And
Be positioned at the Avidin layer on the closure layer;
Wherein in closure layer and Avidin layer, the quantity of biotin is the 0.15-0.4 of Avidin active unit.
2. solid phase carrier as claimed in claim 1 is characterized in that, described solid phase carrier substrate is selected from down group: glass sheet, plastic sheet, nitrocellulose membrane, PDVF film.
3. solid phase carrier as claimed in claim 1 is characterized in that, the total content of described Avidin-biotin is 5-1000ug/cm
2
4. solid phase carrier as claimed in claim 1 is characterized in that, described Avidin is selected from down group: white of an egg Avidin, Streptavidin, and composition thereof.
5. solid phase carrier as claimed in claim 1 is characterized in that, described biotin is selected from down group: biotin N-maloyl imines ester, long-armed biotin or its potpourri.
6. the preparation method of the described protein-chip solid phase carrier of claim 1 is characterized in that, comprises step:
(a) a solid phase carrier substrate is soaked in the biotin labeled closure solution,
(b) solid phase carrier of usefulness damping fluid washing step (a);
(c) solid phase carrier of drying steps (b);
(d) solid phase carrier with step (c) is soaked in the Avidin solution, and wherein to make the quantity of biotin be the 0.15-0.4 of Avidin active unit to the concentration of Avidin,
(e) solid phase carrier of usefulness damping fluid washing step (d);
(f) solid phase carrier of drying steps (e).
7. method as claimed in claim 6 is characterized in that, described solid phase carrier is selected from down group: glass sheet, plastic sheet, nitrocellulose membrane, PDVF film.
8. method as claimed in claim 5 is characterized in that, in the described Avidin solution Avidin concentration be 5-1000ug/ml.
9. method as claimed in claim 6 is characterized in that, described Avidin is selected from down group: white of an egg Avidin, Streptavidin, and composition thereof; And described biotin is selected from down group: biotin N-maloyl imines ester, long-armed biotin or its potpourri.
10. method as claimed in claim 6 is characterized in that, step (a) and (d) soaking conditions be under the room temperature 90-150 minute, or 4 ℃ are spent the night; And drying condition is room temperature airing or freeze drying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB03116076XA CN100341570C (en) | 2003-03-31 | 2003-03-31 | Preparation method of protein chip |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB03116076XA CN100341570C (en) | 2003-03-31 | 2003-03-31 | Preparation method of protein chip |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1534295A true CN1534295A (en) | 2004-10-06 |
| CN100341570C CN100341570C (en) | 2007-10-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB03116076XA Expired - Fee Related CN100341570C (en) | 2003-03-31 | 2003-03-31 | Preparation method of protein chip |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102439447A (en) * | 2009-03-02 | 2012-05-02 | 日本烟草产业株式会社 | Method for detecting substance in biological sample |
| CN102539740A (en) * | 2010-12-29 | 2012-07-04 | 河北省健海生物芯片技术有限责任公司 | Protein chip and method for detecting 80 kinds of autoantibodies simultaneously |
| CN101929997B (en) * | 2008-12-26 | 2014-03-19 | 上海透景生命科技有限公司 | Method for improving sensitivity of immune detection |
| CN108152510A (en) * | 2017-12-15 | 2018-06-12 | 武汉科技大学 | A kind of protein-chip of joint-detection atherosclerosis and its application |
| CN113063940A (en) * | 2021-03-18 | 2021-07-02 | 北京万泰生物药业股份有限公司 | Method for simultaneously detecting multiple antigen antibodies and preparation of carrier thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU7742100A (en) * | 1999-09-29 | 2001-04-30 | Oligos Etc. Inc. | Arrays with modified oligonucleotide and polynucleotide compositions |
| CN1338633A (en) * | 2001-09-29 | 2002-03-06 | 上海晶泰生物技术有限公司 | Protein chip for diagnosing autoimmune diseases |
| CN1156702C (en) * | 2001-07-11 | 2004-07-07 | 上海晶泰生物技术有限公司 | Protein chip based on labeling streptavidin-biotin technology |
-
2003
- 2003-03-31 CN CNB03116076XA patent/CN100341570C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101929997B (en) * | 2008-12-26 | 2014-03-19 | 上海透景生命科技有限公司 | Method for improving sensitivity of immune detection |
| CN102439447A (en) * | 2009-03-02 | 2012-05-02 | 日本烟草产业株式会社 | Method for detecting substance in biological sample |
| CN102539740A (en) * | 2010-12-29 | 2012-07-04 | 河北省健海生物芯片技术有限责任公司 | Protein chip and method for detecting 80 kinds of autoantibodies simultaneously |
| CN108152510A (en) * | 2017-12-15 | 2018-06-12 | 武汉科技大学 | A kind of protein-chip of joint-detection atherosclerosis and its application |
| CN113063940A (en) * | 2021-03-18 | 2021-07-02 | 北京万泰生物药业股份有限公司 | Method for simultaneously detecting multiple antigen antibodies and preparation of carrier thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100341570C (en) | 2007-10-10 |
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