CN104931694B - A kind of small-molecular micro-array based on isocyanates and preparation method thereof - Google Patents
A kind of small-molecular micro-array based on isocyanates and preparation method thereof Download PDFInfo
- Publication number
- CN104931694B CN104931694B CN201510343984.8A CN201510343984A CN104931694B CN 104931694 B CN104931694 B CN 104931694B CN 201510343984 A CN201510343984 A CN 201510343984A CN 104931694 B CN104931694 B CN 104931694B
- Authority
- CN
- China
- Prior art keywords
- chip substrate
- small
- solution
- small molecule
- isocyanate
- 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.)
- Active
Links
Classifications
-
- 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
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
Landscapes
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention belongs to biochip technology field, specifically discloses a kind of small-molecular micro-array and preparation method thereof.After the method modifies hydrophilic backbone polymer on chip substrate, the terminal of polymer is modified to into isocyanate groups.Up to ten thousand kinds of different small molecules are selected and are imprinted on the substrate of isocyanate groups modification and through high-temperature post-treatment, prepare small-molecular micro-array.The method is fast and efficiently fixed on the small molecule for arbitrarily having nucleophilic group on the chip substrate of isocyanate-modified using the reaction between various nucleophilic groups such as isocyanate groups and amino, hydroxyl.Small-molecular micro-array prepared by the present invention, simple with preparing, small molecule fixed efficiency is high, and anti-non-specific adsorption ability is strong, and flux is high, the advantages of sample consumption is few, has broad application prospects in terms of high-flux medicaments sifting.
Description
Technical field
The invention belongs to biochip technology field, and in particular to a kind of small-molecular micro-array and preparation method thereof.
Background technology
Small-molecular micro-array refers to that form fixes the highdensity of small molecule formation on solid substrate in a regular array
Microarray, with the outstanding advantages such as high flux, extensive, concurrency, sample consumption be few, be study small molecule interaction,
Living things catalysis process, protein science and drug discovery etc. are there is provided powerful instrument.
Small-molecular micro-array by it is substantial amounts of with different structure and not isoplastic small molecule be fixed on modification after chip
On substrate, it is desirable to be expeditiously fixed on small molecule on substrate and do not destroy the characteristic combined with target protein by small molecule.Mesh
Before, selective covalently fixing means and selective non-covalent fixing means are to prepare the modal method of small-molecular micro-array, such as
The covalent reaction that epoxides can be passed through with hydrazides group optionally fixes the small molecule containing hydrazides group, or by anti-
Strong noncovalent interaction between streptavidin and biotin optionally fixes the small molecule containing biotin.Choosing
Compound with groups such as amino, hydroxyl, sulfydryl, carboxyls is successfully fixed on carrier surface by selecting property fixing means,
For the research of array of small molecules plays an important role.But, the problem that selective fixing means is present is, small molecule
Compound must have certain specific group just to can connect on substrate surface.The small molecule of synthesis in solid state can in building-up process
To connect upper certain group, but the small molecule in the small molecule libraries that possess of the mechanism such as natural products or pharmaceuticals has various
Different chemical constitutions and group, therefore above-mentioned small molecule can not be fixed using selective fixing means, it is nonselective solid
The method of determining can overcome these shortcomings to a certain extent.
One of nonselective fixing means is photo-crosslinking surface chemistry（Kanoh, N., et al.
Immobilization of naturalproducts on glass slides by using a photoaffinity
reaction and the detection of protein-small-molecule interactions.
Angew.Chem. Int. Ed. Engl. 42, 5584–5587,2003）, consolidated using the Cabbeen intermediate of high reaction activity
Fixed each micromolecular.But there is more false positive in this non-selective fixing means.Another kind of non-selective fixing means
It is fixing the small molecule arbitrarily with nucleophilic group using isocyanate groups（Bradner, J. E.et al., A
robust small-molecule microarray platform for screening cell lysates, Chem
Biol 13, 493–504, 2006）But, the isocyanates surface to the fixed efficiency of the groups such as carboxyl, secondary hydroxyl group very
It is low, only the 10% of amino fixed efficiency.Research expeditiously, the microarray preparation method that can fix various small molecules be little
The wide variety of premise of molecular microarray and basis.
The content of the invention
It is an object of the invention to provide a kind of pervasive, efficient, little point be fixed on small molecule on chip substrate
Sub- microarray and preparation method thereof.Compared with the preparation method of Bradner et al., the present invention provide preparation method to carboxyl,
The fixed efficiency of the group weaker with isocyanates reactivity such as secondary hydroxyl group improves 2 ~ 3 times.
The preparation method of the small-molecular micro-array that the present invention is provided, concretely comprises the following steps：
（1）By hydrophilic backbone polymer in chip substrate surface modification；
（2）Hydrophilic backbone polymer terminal is modified to into isocyanate groups；
（3）Small molecule solution point is printed on handled chip, chip substrate is post-processed after being dried, and obtains little point
Sub- microarray.
In the present invention, described isocyanate groups are polyfunctional isocyanate compounds, and a part of functional group is used for will
Polyfunctional isocyanate is covalently attached on hydrophilic backbone polymer, and remaining functional group is used to provide free NCO
Group.
In the present invention, described polyfunctional isocyanate compound is aromatic poly-isocyanate compound.Compare fat
Race's isocyanate compound, aromatic isocyanate compound reactivity are higher, it is easier to which hydroxyl, carboxyl etc. react.Therefore,
Using aromatic isocyanate compound modify chip substrate, can with nucleophilic group（Amino, hydroxyl, sulfydryl, carboxyl
Deng）Small molecule more efficiently covalent bond, so as to improve fixed efficiency.
In the present invention, described aromatic poly-isocyanate compound be PPDI, toluene di-isocyanate(TDI),
'-diphenylmethane diisocyanate, naphthalene diisocyanate, XDI and their mixture.In aromatic series
Preferred PPDI in PIC.
In the present invention, described hydrophilic backbone polymer is the polyalcohol of fluorenylmethyloxycarbonyl protection.Hydrophilic skeleton compound
With two functions, the first makes fixed small molecule apart from solid chip substrate surface certain distance, reduces substrate surface resistance
Gear small molecule ties the possibility in site.Which two is to provide water-wetted surface, effectively suppresses non-specific adsorption.
In the present invention, the polyalcohol of described fluorenylmethyloxycarbonyl protection is polyethylene glycol（PEG）, polypropylene glycol（PPG）Or
Its copolymer.It is preferred that polyethylene glycol.
In the present invention, chain length n of described polyalcohol is 1 ~ 40.
In the present invention, described post processing is heating post processing.Heating can accelerate isocyanate groups and nucleophilic
The reaction rate of group, with adopting in pyridine vapor compared with the post-processing approach of catalytic treatment, it is possible to obtain higher fixation
Efficiency, and efficiently solve the problems, such as the small molecule point of sample disperse that pyridine vapor catalytic treatment is caused.
In the present invention, described heating post processing is 40 DEG C ~ 50 DEG C and heats in atmosphere or 40 DEG C ~ 50 DEG C
Heat in nitrogen.
In the present invention, described chip substrate is glass, silicon chip, plastics, quartz, gel or nylon membrane.Substrate surface one
As be amino group, can be by being covalently attached hydrophilic backbone polymer with the reaction of carboxyl.
Used as exemplary, the specific operation process of preparation method of the present invention is as follows：
First, prepare hydrophilic backbone polymer solution, solvent is dimethylformamide, skeleton polymer concentration be 100uM ~
10mM；Hexafluorophosphoric acid BTA -1- bases-epoxide tripyrrole alkyl concentration is 0.2mM ~ 20mM；DIPEA
Concentration is 2mM ~ 200mM；Chip substrate is immersed in prepared solution, 5 ~ 20 hours of reaction are stirred at room temperature,
The skeleton polymer that chip substrate surface modification is protected with fluorenylmethyloxycarbonyl；
2nd, deprotection solution is prepared, solvent is dimethylformamide, and reaction reagent is piperidines, piperidines and dimethyl formyl
The volume ratio of amine is 0.001 ~ 0.1；The chip substrate that step one is processed is immersed in piperidine solution, reaction 5 is stirred at room temperature
~ 24 hours, make chip substrate surface deprotection be free amino group group；
3rd, prepare aromatic poly-isocyanate compound solution, solvent is dimethylformamide, aromatic poly-isocyanate
Compound concentration is 6mM ~ 600mM；The chip substrate of step 2 process is immersed in into aromatic poly-isocyanate compound molten
In liquid, 0.1 ~ 10 hour of reaction is stirred at room temperature, makes chip substrate surface modification be isocyanate groups；
4th, small molecule solution is prepared, solvent is dimethyl sulfoxide (DMSO), and small molecule solution concentration is 10 μM ~ 100mM；Will be little
Molecular solution is imprinted on the chip substrate of step 3 preparation using contact point model machine point；After being dried chip substrate, by chip base
Piece is post-processed, and finishing time is 5 ~ 40 hours, obtains small-molecular micro-array.
The present invention also provides a kind of small-molecular micro-array, including：
（1）Chip substrate is used as solid support；
（2）Chip substrate surface connects one layer of hydrophilic backbone polymer；
（3）Hydrophilic backbone polymer surface connects one layer of polyfunctional isocyanate compound, the polyfunctional isocyanate
Compound is by isocyanates covalent bond hydrophilic backbone polymer, and provides free isocyanate groups group；
（4）Isocyanate groups surface is covalently attached small molecule, and described small molecule is distributed in institute by array format is discrete
On the chip substrate of process.
In the present invention, described isocyanate groups are polyfunctional isocyanate compounds.
In the present invention, described polyfunctional isocyanate compound is aromatic poly-isocyanate compound.
In the present invention, described aromatic poly-isocyanate compound be PPDI, toluene di-isocyanate(TDI),
'-diphenylmethane diisocyanate, naphthalene diisocyanate, XDI and their mixture.In aromatic series
Preferred PPDI in PIC.
In the present invention, described hydrophilic backbone polymer is the polyalcohol of fluorenylmethyloxycarbonyl protection.
In the present invention, the polyalcohol of described fluorenylmethyloxycarbonyl protection is polyethylene glycol（PEG）, polypropylene glycol（PPG）Or
Its copolymer.It is preferred that polyethylene glycol.
In the present invention, chain length n of described polyalcohol is 1 ~ 40.
In the present invention, described chip substrate is glass, silicon chip, plastics, quartz, gel or nylon membrane.
Small-molecular micro-array proposed by the present invention and preparation method thereof is more with amino, hydroxyl etc. based on isocyanate groups
Reaction between kind of nucleophilic group, by using aromatic isocyanate compound and heating high-temperature post-treatment method, will be various little
Molecule is expeditiously fixed on chip substrate.It is particularly with the hydroxyl weaker with isocyanate groups reaction and carboxyl, fixed
Efficiency improves 2 ~ 3 times.Small-molecular micro-array prepared by the present invention, simple with preparing, small molecule fixed efficiency is high, resists non-specific
Property high adsorption capacity, flux is high, the advantages of sample consumption is few, has broad application prospects in terms of high-flux medicaments sifting.
Description of the drawings
Fig. 1 small-molecular micro-array preparation method schematic flow sheets.
Biotin in small-molecular micro-arrays of the Fig. 2 based on PPDI and 45 DEG C of heating post-treatment condition preparations
The mass surface density image of antibody.
In small-molecular micro-arrays of the Fig. 3 based on PPDI and 45 DEG C of heating post-treatment condition preparations, each is biological
The fixed efficiency of plain molecule.
Specific embodiment
The present invention is further described below by specific embodiment：
Embodiment 1：With dimethylformamide as solvent, fluorenes methoxy carbonyl acyl group-six polyethylene glycol of amino-carboxylic acid is prepared molten
Liquid, its concentration are 1mM, and the solution is also containing hexafluorophosphoric acid BTA -1- bases-epoxide tripyrrole alkyl（Its concentration is 2mM）、
DIPEA（Its concentration is 20mM）.Chip substrate is immersed in into methoxy carbonyl acyl group-six polyethylene glycol of amino-carboxylic acid
In solution, 10 hours of reaction are stirred at room temperature.The chip substrate after process is cleaned by solvent of dimethylformamide.Clearly
Chip substrate after washing is put in piperidines deprotection solution, and solvent is the body of dimethylformamide, piperidines and dimethylformamide
Product is stirred at room temperature 12 hours of reaction than being 0.01.Chip substrate is cleaned using dimethylformamide and is put it into benzene two
In isocyanate solution, the solution adopts tetrahydrofuran for solvent, and the concentration of PPDI is 60mM, is stirred at room temperature anti-
Answer 1 hour.The reacted chip substrate thoroughly cleaning in solvent dimethylformamide and tetrahydrofuran solvent successively.Dry
Chip substrate after cleaning, and chip substrate is dried up with nitrogen.Chip substrate through being processed as above is placed in vacuum desiccator
Preserve.
Small molecule solution is prepared, solvent is the mixture of dimethyl sulfoxide (DMSO) or dimethyl sulfoxide (DMSO) and water.Small molecule is distinguished
It is the biotin with amino（Biotin -1）, the biotin with p-nitrophenyl ester（Biotin -2）, the biology with hydrazides
Element（Biotin -3）, the biotin with hydroxyl（Biotin -4）And biotin（Biotin -5）.Solution concentration is 1mM, 4mM,
8mM and 10mM.Each biotin solution is put successively along model machine the chip substrate for being imprinted on isocyanate-modified using contact point
On.Wait the solvent on chip substrate（The mixture of dimethyl sulfoxide (DMSO) or dimethyl sulfoxide (DMSO) and water）After volatilizing completely, by chip
Substrate is placed on 12 hours in 45 DEG C of insulating box, completes the last handling process of chip.Chip substrate through post-processing is placed
Preserve in -20 DEG C of environment.It is the preparation process of small-molecular micro-array above.
In order to study fixed efficiency of the chip substrate of isocyanate-modified to the small molecule with nucleophilic group, will be above-mentioned
Small-molecular micro-array is reacted with biotin antibody, and the mass surface density of biotin antibody is as shown in Fig. 2 different biology
The fixed efficiency of plain molecule is as shown in Figure 3.
As a result show, adopt six polyethylene glycol for skeleton polymer, with PPDI as terminal molecule, adopt 45
DEG C post-treatment condition, can effectively prepare small-molecular micro-array.Wherein, the surface fixed efficiency of carboxyl is 30% or so, is to adopt
With 3 times or so of hexamethylene diisocyanate and the carboxyl surface fixed efficiency for being catalyzed reprocessed substrate.The method
Prepare simple, fixed efficiency height, anti-non-specific adsorption ability, it is ensured that high-quality small-molecular micro-array.
Embodiment 2：With dimethylformamide as solvent ,-ten two polyethylene glycol of fluorenes methoxy carbonyl acyl group amino-carboxylic acid is prepared molten
Liquid, its concentration are 1mM, and the solution is also containing hexafluorophosphoric acid BTA -1- bases-epoxide tripyrrole alkyl（Its concentration is 2mM,
N）, N- diisopropylethylamine（Its concentration is 20mM）.By chip substrate be immersed in-six polyethylene glycol of fluorenes methoxy carbonyl acyl group amino-
In carboxylic acid solution, 5 hours of reaction are stirred at room temperature.The chip substrate after process is carried out clearly by solvent of dimethylformamide
Wash.Chip substrate after cleaning is put in piperidines deprotection solution, and solvent is dimethylformamide, piperidines and dimethylformamide
Volume ratio be 0.01, be stirred at room temperature reaction 5 hours.Chip substrate is cleaned using dimethylformamide and toluene is put it into
In diisocyanate solution, the solution adopts dimethylformamide for solvent, and the concentration of toluene di-isocyanate(TDI) is 60mM, room temperature
Stirring reaction 0.5 hour.Reacted chip substrate is thoroughly clear in solvent dimethylformamide and tetrahydrofuran solvent successively
Wash.The chip substrate after cleaning is dried, and continuation nitrogen dries up chip substrate.Chip substrate through being processed as above is placed on very
Preserve in empty drier.
Small molecule solution is prepared, solvent is the mixture of dimethyl sulfoxide (DMSO) or dimethyl sulfoxide (DMSO) and water.Small molecule is distinguished
It is the biotin with amino（Biotin -1）, the biotin with p-nitrophenyl ester（Biotin -2）, the biology with hydrazides
Element（Biotin -3）, the biotin with hydroxyl（Biotin -4）And biotin（Biotin -5）.Solution concentration is 1mM, 4mM,
8mM and 10mM.Each small molecule is put successively along model machine using contact point and be imprinted on the chip substrate of isocyanate-modified.
Wait the solvent on chip substrate（The mixture of dimethyl sulfoxide (DMSO) or dimethyl sulfoxide (DMSO) and water）After volatilizing completely, by chip substrate
12 hours in 40 DEG C of insulating box are placed on, the last handling process of chip is completed.Chip substrate through post-processing is positioned over -20
Preserve in DEG C environment.It is the preparation process of small-molecular micro-array above.
The foregoing is only presently preferred embodiments of the present invention, all impartial changes done according to scope of the present invention patent with
Modification, should all belong to the covering scope of the present invention.
Claims (3)
1. a kind of preparation method of small-molecular micro-array, it is characterised in that concretely comprise the following steps：
（1）By hydrophilic backbone polymer in chip substrate surface modification；
（2）Hydrophilic backbone polymer terminal is modified to into isocyanate groups；
（3）Small molecule solution point is printed on the chip of above-mentioned process, chip substrate carries out heating post processing after being dried, and obtains little
Molecular microarray；
Described isocyanate groups are polyfunctional isocyanate compounds；
Described polyfunctional isocyanate compound is selected from following aromatic poly-isocyanate compound：PPDI,
Toluene di-isocyanate(TDI), '-diphenylmethane diisocyanate, naphthalene diisocyanate, XDI and they
Mixture；
Described hydrophilic backbone polymer is the polyalcohol of fluorenylmethyloxycarbonyl protection；
The polyalcohol of described fluorenylmethyloxycarbonyl protection is polyethylene glycol, polypropylene glycol or its copolymer；
Chain length n of described polyalcohol is 1 ~ 40；
Described heating post processing is 40 DEG C ~ 50 DEG C and heats in atmosphere or 40 DEG C ~ 50 DEG C heating in nitrogen
Process.
2. the preparation method of small-molecular micro-array according to claim 1, it is characterised in that specific operation process is as follows：
First, prepare hydrophilic backbone polymer solution, solvent is dimethylformamide, skeleton polymer concentration be 100uM ~
10mM；Hexafluorophosphoric acid BTA -1- bases-epoxide tripyrrole alkyl concentration is 0.2mM ~ 20mM；DIPEA
Concentration is 2mM ~ 200mM；Chip substrate is immersed in the solution, 5 ~ 20 hours of reaction, chip base is stirred at room temperature
Piece surface modification is the skeleton polymer with fluorenylmethyloxycarbonyl protection；
2nd, deprotection solution is prepared, solvent is dimethylformamide, and reaction reagent is piperidines, piperidines and dimethylformamide
Volume ratio is 0.001 ~ 0.1；The chip substrate that step one is processed is immersed in piperidine solution, reaction 5 ~ 24 is stirred at room temperature
Individual hour, makes chip substrate surface deprotection be free amino group group；
3rd, prepare aromatic poly-isocyanate compound solution, solvent is dimethylformamide, aromatic poly-isocyanate chemical combination
Thing concentration is 6mM ~ 600mM；The chip substrate of step 2 process is immersed in aromatic poly-isocyanate compound solution,
0.1 ~ 10 hour of reaction is stirred at room temperature, makes chip substrate surface modification be isocyanate groups；
4th, small molecule solution is prepared, solvent is dimethyl sulfoxide (DMSO), and small molecule solution concentration is 10 μM ~ 100mM；By small molecule
Solution is imprinted on the chip substrate of step 3 preparation using contact point model machine point；After being dried chip substrate, chip substrate is entered
Row post processing, finishing time is 5 ~ 40 hours, obtains small-molecular micro-array.
3. a kind of small-molecular micro-array prepared by preparation method described in claim 1, it is characterised in that include：
（1）Chip substrate is used as solid support；
（2）Chip substrate surface connects hydrophilic backbone polymer；
（3）Hydrophilic backbone polymer surface connects polyfunctional isocyanate compound, and the polyfunctional isocyanate compound is led to
Isocyanates covalent bond hydrophilic backbone polymer is crossed, and free isocyanate group group is provided；
（4）Isocyanate groups surface is covalently attached small molecule, described small molecule by array format it is discrete be distributed in it is handled
Chip substrate on.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510343984.8A CN104931694B (en) | 2015-06-22 | 2015-06-22 | A kind of small-molecular micro-array based on isocyanates and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510343984.8A CN104931694B (en) | 2015-06-22 | 2015-06-22 | A kind of small-molecular micro-array based on isocyanates and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104931694A CN104931694A (en) | 2015-09-23 |
| CN104931694B true CN104931694B (en) | 2017-03-29 |
Family
ID=54118960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510343984.8A Active CN104931694B (en) | 2015-06-22 | 2015-06-22 | A kind of small-molecular micro-array based on isocyanates and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104931694B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107202893B (en) * | 2016-03-16 | 2019-08-13 | 广州高通生物技术有限公司 | A kind of small molecule chip, its construction method, its application and its detection method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101024856A (en) * | 2007-01-30 | 2007-08-29 | 华东理工大学 | Method for preparing small-molecular micro-array |
| CN101048661A (en) * | 2004-08-17 | 2007-10-03 | 生物概念股份有限公司 | Protein microarrays |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070134784A1 (en) * | 2005-12-09 | 2007-06-14 | Halverson Kurt J | Microreplicated microarrays |
| HUP0600668A2 (en) * | 2006-08-22 | 2008-02-28 | Avicor Kft | Active carrier, process for producing thereof and the use of thereof |
-
2015
- 2015-06-22 CN CN201510343984.8A patent/CN104931694B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101048661A (en) * | 2004-08-17 | 2007-10-03 | 生物概念股份有限公司 | Protein microarrays |
| CN101024856A (en) * | 2007-01-30 | 2007-08-29 | 华东理工大学 | Method for preparing small-molecular micro-array |
Non-Patent Citations (2)
| Title |
|---|
| A robust small-molecule microarray platform for screening cell lysates;James E. Bradner等;《Chemistry & Biology》;20060531;第13卷(第5期);第493-504页 * |
| 芯片表面异氰酸酯基硅烷自组装膜的制备及表征;谢瑶等;《科学通报》;20080930;第53卷(第18期);第2191-2194页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104931694A (en) | 2015-09-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6174683B1 (en) | Method of making biochips and the biochips resulting therefrom | |
| US7695910B2 (en) | Method for manufacturing hydrogel biochip by using star-like polyethylene glycol derivative having epoxy group | |
| JP2004533500A5 (en) | ||
| JPH0823975A (en) | Material for immobilizing biologically active substance and immobilizing method | |
| EP1377369B1 (en) | Substrates, preparation and use | |
| EP1715039A1 (en) | Method of isolating a nucleic acid using a bifunctional material containing an amino group and a carboxyl group | |
| CN104931694B (en) | A kind of small-molecular micro-array based on isocyanates and preparation method thereof | |
| WO2004056846A2 (en) | Special film-coated substrate for bio-microarray fabrication and use thereof | |
| US7611889B2 (en) | Method for noncovalently immobilizing a biomolecule on a solid substrate and microarray produced according to the method | |
| JP2003517589A (en) | Molecular microarrays and methods for their production and use | |
| EP1644527B9 (en) | Cucurbituril derivative-bonded solid substrate and biochip using the same | |
| JP4704325B2 (en) | Microarray substrate and manufacturing method thereof | |
| JP4197279B2 (en) | Biologically-derived substance detection substrate and manufacturing method thereof | |
| CN102168146A (en) | High-specificity and high-sensitivity gene chip as well as preparation method and application thereof | |
| CN104931687A (en) | Three-dimensional biological surface, preparation method thereof, three-dimensional biological chip and application of three-dimensional biological chip | |
| CN110055318A (en) | A kind of preparation method of the three dimensional DNA microarray surface based on click chemistry | |
| KR100450822B1 (en) | A method of preparing a hydrogel biochip by using satar-like PEG derivatives | |
| KR20050014409A (en) | Substrate for immobilizing physiological material, and a method of preparing the same | |
| US6500921B1 (en) | Schiff base reductant co-dispense process | |
| West | Modification of materials with bioactive peptides | |
| KR100829574B1 (en) | Microarray substrate method of analyzing biomolecule using the microarray substrate and lab-on-a-chip including the microarray substrate | |
| JP5093661B2 (en) | Substrates for sensing biological substances and methods for recovering or detecting proteins, metal ions, etc. using the same | |
| Santiago et al. | A robust affinity chromatography system based on ceramic monoliths coated with poly (amino acid)‐based polymeric constructs | |
| ES2245899B1 (en) | SOLID SUPPORT FOR THE UNION AND / OR CHEMICAL SYNTHESIS IN SOLID PHASE AND PROCEDURE OF USE. | |
| CN116446055A (en) | Preparation method and application of substrate with high-density reaction sites |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |