CN105837730B - Method for constructing bioactive surface by combining layer-by-layer assembly technology and host-guest interaction - Google Patents
Method for constructing bioactive surface by combining layer-by-layer assembly technology and host-guest interaction Download PDFInfo
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- CN105837730B CN105837730B CN201610183773.7A CN201610183773A CN105837730B CN 105837730 B CN105837730 B CN 105837730B CN 201610183773 A CN201610183773 A CN 201610183773A CN 105837730 B CN105837730 B CN 105837730B
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Classifications
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- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
The invention relates to the field of biomedical engineering and high polymer materials, and provides a method for constructing a bioactive surface by combining a layer-by-layer assembly technology and host-guest interaction. The invention introduces an object molecule adamantane (Ada) group to polyacrylic acid (PAA) through a simple copolymerization technology to obtain a copolymer (P (AA-Ada)) of an acrylic acid monomer and an acrylic acid adamantane methanol ester monomer; and then depositing the polyelectrolyte multilayer film of P (AA-Ada) and Polyacrylamide (PAH) on the surfaces of various aminated base materials by utilizing a layer-by-layer assembly (LbL) technology. Beta-cyclodextrin (beta-CD) derivatives of different biomolecules can be fixed and modified at high density by utilizing a large amount of adamantyl groups contained in the polyelectrolyte multilayer film, so that a bioactive surface with corresponding functions is obtained. The invention has the outstanding characteristics that: the method has universality and can be applied to base materials with different chemical properties and shapes; and the constructed bioactive surface has adjustable performance, and is suitable for wider biomedical fields.
Description
Technical field
The present invention relates to bio-medical functional high polymer material field, and in particular to one kind combines laminated assembling technology and master
Object interaction builds the preparation method of bioactivity surface on a variety of base materials.
Background technology
Bioactivity surface refers to the biologically functional molecules such as protein, polypeptide, nucleic acid, polysaccharide passing through physically or chemically side
Method is fixed on synthetic surfaces, and then assigns the specific bioactive functions in surface(Such as biomolecule recognition performance, sterilization
Performance, anticoagulation function, antifouling property etc.), this is in many bio-medical engineerings and biological technical field extensive application.Cause
How simply, efficiently, pervasively to biomaterial this, carry out surface modification significant to build bioactivity surface.
The structure of usual bioactivity surface is, first in material surface one layer of matrix of formation, then biologically functional molecule to be fixed or born
It is loaded in matrix.Polymer is due to its good biocompatibility, and with multiple avtive spots, feature is strong, it is easy to surface modification etc.
Advantage is widely adopted as matrix.The polymer substrate preparation method generally used mainly includes self assembly, Langmuir-
Blodgett films, polymer coating, surface initiation polymerization, laminated assembling technology etc..Among these, laminated assembling technology is a kind of base
The polymer alternating layers with different electric charges are adsorbed to the method for modifying in substrate surface in electrostatic interaction.With its other party
Method is compared, and laminated assembling technology has simple to operate, polymer film parameter is convenient to control, almost go for any shape and
A variety of advantages such as the base material of physical property.Especially, the polymer film of laminated assembling technology formation has three-dimensional structure, fits very much
Load immobilizing biologically active molecule is closed, by simply changing the thickness of multilayer film, fixed biological point just can be efficiently controlled
The quantity of son.
In the common methods of material surface it is that biomolecule is passed through by covalent bond using chemical method by biomolecule fixation
With reference in matrix.Although this method adhesion is stronger, the operation of complexity is usually required and using organic solvent etc..In recent years
Come, widely paid close attention to using the affine fixation based on weak interaction.Host-guest interaction is a kind of common oversubscription
Sub- chemical action, in advance by host molecule(Or guest molecule)Modified after biomolecule, just can be mutual by Subjective and Objective
The fixation of biomolecule is easily realized in effect under mild conditions.Beta-schardinger dextrin(β-CD)It is a kind of common main body point
Son, its hydrophobic cavity facilitates the insertion of a variety of guest molecules.β-CD itself have the hydroxyls of multiple convenient activation, can be with
Realize on a molecule combine multiple biological micromolecule parts so that improve local ligand density and then so that after modify β-
CD has higher bioactivity.In addition, chemically angle is set out, modification obtains having difference after we can be carried out to β-CD
The β-cdderivatives of function., can be by simply mixing after two kinds or even various biomolecules using host-guest interaction
The β-cdderivatives of modification, are realized difunctional or even multi-functional on the same surface of imparting.
The present invention is from the conventional polyanion/polycation of layer assembly to poly propenoic acid allylamine(PAA/PAH)
With typical Subjective and Objective to beta-schardinger dextrin/adamantane(β-CD/Ada)It is used as model.First will by simple combined polymerization technology
Ada groups, which are incorporated on polyanion PAA, obtains copolymer p (AA-Ada), then using laminated assembling technology in a variety of base materials
Surface deposition P (AA-Ada)/PAH multilayer films, the β-CD of bioactive molecule will be modified with finally by host-guest interaction
It is incorporated into and the bioactivity surface with corresponding function is obtained in polyelectrolyte multilayer film.
The content of the invention
The technical problems to be solved by the invention are:For the reaction present in current bioactivity surface preparation method
The problem of journey is complicated, base material is limited, immobilizing biologically active molecular species is limited, function is single there is provided one kind it is simple to operate, have
Universality, multiple biological activities molecule can be fixed, the surface modifying method of a variety of biological functions in surface is assigned.
The present invention solves its technical problem and uses following technical scheme:
A kind of structure that the present invention is provided has the preparation method of the material of correspondence biological function, it is characterised in that including
Following steps:
(1)The preparation of polyelectrolyte multilayer film modified surface:
Amidized base material is immersed in the copolymer (P of acrylic monomers and 1- acrylic acid adamantane methanol ester monomers
(AA-Ada) a period of time in solution), a period of time in polypropylene amine (PAH) solution is then immersed in again, i.e., in amination
Substrate surface obtain one layer of P (AA-Ada)/PAH bilayer, immersion is repeated several times, if being had dried layer P (AA-
Ada the polyelectrolyte multilayer film modified surface of)/PAH bilayers;
(2)Polyelectrolyte multilayer film modified surface immobilizing biologically active molecule:
Gained is placed in polyelectrolyte multilayer film modified surface and spread out containing the β-CD for having modified bioactive molecule
Reacted in biological solution, that is, obtain being fixed with the polyelectrolyte multilayer film modified surface of bioactive molecule.
Another structure that the present invention is provided has the preparation method of the material of correspondence biological function, it is characterised in that bag
Include following steps:
(1)The preparation of polyanion P (AA-Ada) containing adamantane group:
By certain mol ratio by acrylic monomers, 1- acrylic acid adamantane methanol ester monomer, chain-transferring agent and initiator
It is added in reaction solution and carries out polymerisation, the method purified after reaction using sedimentation separation is produced containing adamantane group
Polyanion P (AA-Ada);
(2)The preparation of polyelectrolyte multilayer film modified surface:
Amidized base material is immersed in the copolymer (P of acrylic monomers and 1- acrylic acid adamantane methanol ester monomers
(AA-Ada) a period of time in solution), a period of time in polypropylene amine (PAH) solution is then immersed in again, i.e., in amination
Substrate surface obtain one layer of P (AA-Ada)/PAH bilayer, immersion is repeated several times, if being had dried layer P (AA-
Ada the polyelectrolyte multilayer film modified surface of)/PAH bilayers;
(3)Polyelectrolyte multilayer film modified surface immobilizing biologically active molecule:
Gained is placed in polyelectrolyte multilayer film modified surface and spread out containing the β-CD for having modified bioactive molecule
Reacted in biological solution, that is, obtain being fixed with the polyelectrolyte multilayer film modified surface of bioactive molecule.
Further, described bioactive molecule is biotin, mannose or arginine-glutamic acid-aspartic acid-figured silk fabrics ammonia
Sour polypeptide.
Further, the preparation process for being modified with the β-cdderivatives of the biotin molecule is:By propargyl biotin and 7
β-the CD of individual azido group modification(β-CD-(N3)7)Click-reaction is carried out, the β-CD of biotin modification are made.
Further, the preparation process for being modified with the β-cdderivatives of the mannose molecules is:By propargyl mannose and 7
β-the CD of individual azido group modification(β-CD-(N3)7)Click-reaction is carried out, the β-CD of mannose-modified are made.
Further, the β-cdderivatives of the arginine-glutamic acid-aspartic acid-valine peptide molecule are modified with
Preparation process is:By propargyl-arginine-glutamic acid-aspartic acid-valine polypeptide and the β-CD of 7 azido group modifications
(β-CD-(N3)7)Click-reaction is carried out, the peptide modified β-CD of arginine-glutamic acid-aspartic acid-valine are made.
Further, the amidized base material be monocrystalline silicon or glass, the amidized monocrystalline silicon piece or sheet glass
Preparation process is:Monocrystalline silicon piece or sheet glass are placed in 3- aminopropyls-triethoxysilane(APTES)Toluene solution in it is anti-
The monocrystalline silicon or glass baseplate of surface amination should be obtained for a period of time.
Further, the amidized base material is gold-plated monocrystalline silicon piece, the preparation of the amidized gold-plated monocrystalline silicon piece
Process is:Gold-plated monocrystalline silicon piece is placed in the aqueous solution of mercaptoethylamine hydrochloride and reacts a period of time, surface amination is obtained
Gold-plated single crystal silicon substrate.
Further, modified bioactive molecule β-cdderivatives solution for the aqueous solution, phosphate buffer solution or
Other can dissolve the solution of corresponding bioactive molecule.
Further, described to be polymerized to Invertible ideal, the chain-transferring agent is 2-(Phenyl first
Acyl sulfenyl)Propionic acid;Described initiator is azodiisobutyronitrile, ABVN, dibenzoyl peroxide, the carbon of peroxidating two
Sour ethylhexyl, isopropyl benzene hydroperoxide, potassium peroxydisulfate-sulphite system or hydrogen peroxide-perferrite system.
Further, the solution containing chain-transferring agent is DMF solution, the solution containing initiator
For N,N-dimethylformamide solution.
Further, the β-CD of 7 azido group modifications(β-CD-(N3)7)Preparation method be:First by No. six positions of β-CD
Hydroxyl carries out bromine substitution(β-CD-(Br)7)Or iodine substitution(β-CD-(I)7), then carry out Azide with sodium azide.
A kind of structure that the present invention is provided has the preparation method of the material of correspondence biological function, and it includes having in detailed below
Body step:
(1)The preparation of polyanion P (AA-Ada) containing adamantane group:
In reaction unit, acrylic monomers, 1- acrylic acid adamantane methanol ester monomer, chain are turned by certain mol ratio
Move agent and initiator is added in reaction solution, under nitrogen protection stirring reaction, reaction temperature is 65 DEG C, the reaction time is 24 small
When;Reaction is settled after terminating with ether, and the polyanion P (AA-Ada) containing adamantane group can be obtained after separating-purifying;
The P (AA-Ada) is the english abbreviation of the copolymer of 1- acrylic acid adamantane methanol ester monomer and acrylic monomers;
The chain-transferring agent is 2-(Phenyl formyl sulfenyl)Propionic acid;Described initiator is azodiisobutyronitrile etc.;
Described reaction solution is DMF solution.
(2)The preparation of polyelectrolyte multilayer film modified surface:
Prepare polyelectrolyte solution, including polyanion P (AA-Ada) solution and polycation PAH solution;By amination
Base material be immersed in P (AA-Ada) solution, through over cleaning remove combine weaker polymer after be immersed in again in PAH solution,
P (AA-Ada)/PAH bilayer can be obtained on surface after over cleaning, this process repeated several times is finally reached
The number of plies needed, obtains polyelectrolyte multilayer film modified surface;
Described polyelectrolyte solution is acetic acid/sodium acetate buffer that pH value is 5.0;Taken from polyelectrolyte solution
The cleaning solution on the surface gone out is acetic acid/sodium acetate buffer that pH value is 5.0;The amidized base material be monocrystalline silicon,
Glass or gold-plated monocrystalline silicon.
The preparation process of the amidized base material comprises the following steps:
(a)Clean monocrystalline silicon piece or sheet glass are first used into " piranha " solution(Sulfuric acid:Hydrogen peroxide=7:3, volume ratio)
Pre-processed, be subsequently placed in 3- aminopropyls-triethoxysilane(APTES)Toluene solution in react and stay overnight, obtain table
The amidized monocrystalline silicon in face or glass baseplate;
(b)The gold-plated monocrystalline silicon piece ammoniacal liquor that will be cleaned by UV ozone instrument, the mixing of hydrogen peroxide and deionized water is molten
Liquid(Ammoniacal liquor:Hydrogen peroxide:Deionized water=1:1:5, volume ratio)Pre-processed, be subsequently placed in the water of mercaptoethylamine hydrochloride
Reaction is stayed overnight in solution, obtains the gold-plated single crystal silicon substrate of surface amination;
(3)Polyelectrolyte multilayer film modified surface immobilizing biologically active molecule:
The polyelectrolyte multilayer film modified surface of gained is placed in containing the molten of the β-cdderivatives for having modified biomolecule
Reacted in liquid, reaction temperature is room temperature, the reaction time is 12 ~ 24 hours, and reaction cleans surface after terminating with deionized water,
The polyelectrolyte multilayer film modified surface of bioactive molecule can be fixed;
Described bioactive molecule is biotin, mannose and REDV polypeptides;Described has modified bioactive molecule
β-cdderivatives solution for the aqueous solution, phosphate buffer solution or other can dissolve the molten of corresponding bioactive molecule
Liquid.
The preparation process of the β-cdderivatives for being modified with bioactive molecule comprises the following steps:
(a)β-the CD of 7 azido group modifications(β-CD-(N3)7)Preparation;
(b)β-the CD of biotin modification preparation:
In reaction unit, β-CD- (N are first added3)7And biotin-PEG4- alkyne, is then added under nitrogen protection
Catalyst/ligand solution, stirring reaction, reaction temperature is 50 DEG C, and the reaction time is 36 hours, is reacted mixed solution after terminating
Dialysed with MWCO 1000 bag filter, the β-CD of biotin modification are can obtain after freeze-drying.
(c)β-the CD of mannose-modified preparation:
By 1- under nitrogen protection(2 '-propargyl)- α-D-MANNOSE and β-CD- (N3)7Add in catalyst system solution,
Click-reaction is carried out, reaction temperature is 50 DEG C, the reaction time is 24 hours, and reaction removes solvent after terminating, and uses absolute methanol
Precipitation is collected by centrifugation, the β-CD of mannose-modified are can obtain after purification.
(d)β-CD peptide modified REDV preparation:
By propargyl-REDV and β-CD- (N under nitrogen protection3)7Add in catalyst system solution, carry out click-reaction,
Reaction temperature is 50 DEG C, and the reaction time is 24 hours, and post-reaction treatment is to be dialysed using MWCO 500 bag filter, and freezing is dry
It is dry to obtain the peptide modified β-CD of REDV.
It is preferred that, step(a)Described in preparation method be following one or two kinds of:
The hydroxyl of No. six positions of β-CD first is carried out into bromine to replace(β-CD-(Br)7), then carry out Azide with sodium azide;
The hydroxyl of No. six positions of β-CD first is carried out into iodine to replace(β-CD-(I)7), then carry out Azide with sodium azide.
It is preferred that, step(b)Described in catalyst/ligand solution be dimethyl sulphoxide solution, the catalyst/ligand
System is 2,2'- bipyridyls/copper bromide etc..
It is preferred that, step(c)Described in catalyst solution be dimethyl sulphoxide solution, the catalyst/ligand system
For 2,2'- bipyridyls/copper bromide etc..
It is preferred that, step(d)Described in catalyst system solution be dimethyl sulfoxide (DMSO)/water mixed solution, the catalysis
System is copper sulphate/sodium ascorbate etc..
By above-mentioned steps, the biology for finally giving the high density fixed biologically functional molecule with correspondence biological function is living
Property surface.
The present invention has the advantages that following main compared with prior art:
The method that the present invention is provided is that combination laminated assembling technology and host-guest interaction prepare bioactivity surface
Method.Compared with prior art, the present invention has following prominent characteristics:
1. it is simple to operate, easy:Layer assembly and Subjective and Objective reaction condition are gentle, can be under room temperature, aqueous environment
Complete.
2. applicability is wider:The method that laminated assembling technology builds polyelectrolyte multilayer film can apply to different chemistry
Property, base material of different shapes can be realized in any substrate surface containing amino, it is adaptable to such as biological detection, tissue work
Many bio-medical fields such as journey, protein separation.
3. surface property is adjustable:On the one hand can be simply by changing layer assembly number of plies control load biomolecule
Capacity, the β-CD that the modification of different biologically functional molecules on the other hand can be designed as needed assign surface different biological work(
Energy.For example, after fixing the β-CD of biotin modification on the polyelectrolyte multilayer film surface obtained using this method, can be selective
With reference to Avidin(See Fig. 1);, can be with specific absorption canavaline after fixing the β-CD of mannose-modified on surface(Con
A)(See Fig. 2);Fixed on surface after the peptide modified β-CD of REDV, sticking for surface endothelial cell can be promoted(See Fig. 3).
Brief description of the drawings
Fig. 1 is that the β-CD front and rear surfaces of biotin modification are fixed to fluorescent decoration in monocrystalline silicon piece polyelectrolyte multilayer film surface
Avidin absorption situation;
Fig. 2 is that the β-CD front and rear surfaces of mannose-modified are fixed to fluorescence in gold-plated monocrystalline silicon piece polyelectrolyte multilayer film surface
The absorption situation of the canavaline of modification.
Fig. 3 is that table before and after the peptide modified β-CD of REDV is fixed on polyelectrolyte multilayer film surface on gold-plated monocrystalline silicon piece base material
Stick situation in face of endothelial cell.
Embodiment
The method that the combination laminated assembling technology and host-guest interaction that the present invention is provided build bioactivity surface, be
First carry out amination pretreatment to substrate surface, then by polyelectrolyte P (AA-Ada) and PAH by laminated assembling technology on surface
Deposition obtains the polyelectrolyte multilayer film containing Ada groups.The host-guest interaction between Ada and β-CD is finally utilized, in
β-the CD for being modified with different bioactive molecules are fixed on polyelectrolyte multilayer film surface, assign surface corresponding biological function.
Below by embodiment, the present invention is further elaborated, but does not limit the present invention.
Embodiment 1
Being built with reference to laminated assembling technology and host-guest interaction in monocrystalline silicon sheet surface, there is biomolecule to recognize work(
The surface of energy
Monocrystalline silicon piece " piranha " solution that will be cleaned with acetone soln ultrasound(Sulfuric acid:Hydrogen peroxide=7:3, volume
Than)Pre-processed, be subsequently placed in 3- aminopropyls-triethoxysilane(APTES)Toluene solution in react 18 hours, i.e.,
Obtain the monocrystalline silicon piece of surface amination.Polyanion P (AA-Ada) solution and polycation PAH solution, solvent are prepared respectively
The concentration for being 5.0 for pH value is acetic acid/sodium acetate buffer of 0.05 mol/L.Amidized monocrystalline silicon piece is immersed in
In P (AA-Ada) solution, removed through peracetic acid/sodium acetate buffer cleaning after combining weaker polymer and be immersed in PAH again
In solution, P (AA-Ada)/PAH bilayer is obtained on surface after over cleaning, this process repeated several times finally reaches
To the number of plies of needs, you can obtain the monocrystalline silicon piece of polyelectrolyte multilayer film modification.
The hydroxyl of No. six positions of β-CD first is carried out into bromine to replace(β-CD-(Br)7), then carry out Azide system with sodium azide
β-the CD of standby 7 azido groups modification(β-CD-(N3)7);Finally by β-CD- (N3)7Carry out clicking on instead with propargyl biotin
Should, obtain the β-CD of biotin modification(β-CD-(biotin)7).
The monocrystalline silicon piece that above-mentioned polyelectrolyte multilayer film is modified is placed in 1 mM every liter of β-CD- (biotin)7It is water-soluble
In liquid, and reaction is stayed overnight at room temperature.Reaction cleans surface after terminating with water, you can be fixed biotin has biology
The surface of molecular recognition function.
Embodiment 2
Being built with reference to laminated assembling technology and host-guest interaction in gold-plated monocrystalline silicon sheet surface has specific adsorption
The surface of canavaline function
By the gold-plated monocrystalline silicon piece ammoniacal liquor clean with UV ozone instrument is passed through, the mixed solution of hydrogen peroxide and deionized water
(Ammoniacal liquor:Hydrogen peroxide:Deionized water=1:1:5, volume ratio)Pre-processed, be subsequently placed in the water-soluble of mercaptoethylamine hydrochloride
Reaction is stayed overnight in liquid, that is, obtains the gold-plated monocrystalline silicon piece of surface amination.Polyanion P (AA-Ada) solution is prepared respectively and poly-
Cation PAH solution, solvent is acetic acid/sodium acetate buffer that the concentration that pH value is 5.0 is 0.05 mol/L.By amino
The gold-plated monocrystalline silicon piece changed is immersed in P (AA-Ada) solution, is combined through peracetic acid/sodium acetate buffer cleaning removal weaker
Polymer after be immersed in again in PAH solution, P (AA-Ada)/PAH bilayer is obtained on surface after over cleaning,
This process repeated several times finally reaches the number of plies of needs, you can obtain the gold-plated monocrystalline silicon piece of polyelectrolyte multilayer film modification.
The hydroxyl of No. six positions of β-CD first is carried out into bromine to replace(β-CD-(Br)7), then carry out Azide system with sodium azide
β-the CD of standby 7 azido groups modification(β-CD-(N3)7);Finally by β-CD- (N3)7And 1-(2 '-propargyl)- α-D-MANNOSE
Click-reaction is carried out, the β-CD of mannose-modified are obtained(β-CD-(mannose)7).
The gold-plated monocrystalline silicon piece that above-mentioned polyelectrolyte multilayer film is modified is placed in 1 mM every liter of β-CD-
(mannose)7In the aqueous solution, and reaction is stayed overnight at room temperature.Reaction cleans surface after terminating with water, you can be fixed sweet
That reveals sugar has specific adsorption canavaline(Con A)The surface of function.
Embodiment 3
Building to have in gold-plated monocrystalline silicon sheet surface with host-guest interaction with reference to laminated assembling technology promotes endothelium thin
The surface of born of the same parents' adhesive function
By the gold-plated monocrystalline silicon piece ammoniacal liquor clean with UV ozone instrument is passed through, the mixed solution of hydrogen peroxide and deionized water
(Ammoniacal liquor:Hydrogen peroxide:Deionized water=1:1:5, volume ratio)Pre-processed, be subsequently placed in the water-soluble of mercaptoethylamine hydrochloride
Reaction is stayed overnight in liquid, that is, obtains the gold-plated monocrystalline silicon piece of surface amination.Polyanion P (AA-Ada) solution is prepared respectively and poly-
Cation PAH solution, solvent is acetic acid/sodium acetate buffer that the concentration that pH value is 5.0 is 0.05 mol/L.By amino
The gold-plated monocrystalline silicon piece changed is immersed in P (AA-Ada) solution, is combined through peracetic acid/sodium acetate buffer cleaning removal weaker
Polymer after be immersed in again in PAH solution, P (AA-Ada)/PAH bilayer is obtained on surface after over cleaning,
This process repeated several times finally reaches the number of plies of needs, you can obtain the gold-plated monocrystalline silicon piece of polyelectrolyte multilayer film modification.
The hydroxyl of No. six positions of β-CD first is carried out into bromine to replace(β-CD-(Br)7), then carry out Azide system with sodium azide
β-the CD of standby 7 azido groups modification(β-CD-(N3)7);Finally by β-CD- (N3)7Clicked on propargyl-REDV polypeptides
Reaction, obtains the peptide modified β-CD of REDV(β-CD-(REDV)7).
The gold-plated monocrystalline silicon piece that above-mentioned polyelectrolyte multilayer film is modified is placed in 1 mM every liter of β-CD- (REDV)7Water
In solution, and reaction is stayed overnight at room temperature.Reaction cleans surface after terminating with water, you can be fixed having for REDV polypeptides
Promote the surface of adhesion function of monocytes.
This method has potential application prospect in many bio-medicals and technical field of biology.Wherein need to particularly point out
Be that party's science of law is not only limited to us and worked PAA/PAH, the β-CD/Ada of use, and can be generalized to other polymers
With other Subjective and Objectives pair.For needing difunctional or even multifunction surface field, simply it can be introduced altogether using mixing
Mode introduces two or more, and there is the cyclodextrin molecular of different ligands to be achieved.
The desirable embodiment according to the present invention is enlightenment above, by above-mentioned description, and related personnel completely can be with
Without departing from the scope of the technological thought of the present invention', various changes and amendments are carried out.The technical scope of this invention
It is not limited to the content on specification, it is necessary to determine the technical scope according to the scope of the claims.
Claims (10)
1. a kind of method that combination laminated assembling technology and host-guest interaction build bioactivity surface, it is characterised in that
Comprise the following steps:
(1)The preparation of polyelectrolyte multilayer film modified surface:
Amidized base material is immersed in the copolymer p (AA-Ada) of acrylic monomers and 1- acrylic acid adamantane methanol ester monomers
Solution in a period of time, a period of time is then immersed in polypropylene amine PAH solution again, i.e., is obtained in amidized substrate surface
To one layer of P (AA-Ada)/PAH bilayer, immersion is repeated several times, if being had double points of dried layer P (AA-Ada)/PAH
The polyelectrolyte multilayer film modified surface of sublayer;
(2)Polyelectrolyte multilayer film modified surface immobilizing biologically active molecule:
Gained is placed in polyelectrolyte multilayer film modified surface and spread out containing the beta-schardinger dextrin for having modified bioactive molecule
Reacted in biological solution, that is, obtain being fixed with the polyelectrolyte multilayer film modified surface of bioactive molecule.
2. a kind of method that combination laminated assembling technology and host-guest interaction build bioactivity surface, it is characterised in that
Comprise the following steps:
(1)The preparation of polyanion P (AA-Ada) containing adamantane group:
Acrylic monomers, 1- acrylic acid adamantane methanol ester monomer, chain-transferring agent and initiator are added by certain mol ratio
Polymerisation is carried out into reaction solution, the method purified after reaction using sedimentation separation produces poly- the moon containing adamantane group
Ion P (AA-Ada);
(2)The preparation of polyelectrolyte multilayer film modified surface:
Amidized base material is immersed in the copolymer p (AA-Ada) of acrylic monomers and 1- acrylic acid adamantane methanol ester monomers
Solution in a period of time, a period of time is then immersed in polypropylene amine PAH solution again, i.e., is obtained in amidized substrate surface
To one layer of P (AA-Ada)/PAH bilayer, immersion is repeated several times, if being had double points of dried layer P (AA-Ada)/PAH
The polyelectrolyte multilayer film modified surface of sublayer;
(3)Polyelectrolyte multilayer film modified surface immobilizing biologically active molecule:
Gained is placed in polyelectrolyte multilayer film modified surface and spread out containing the beta-schardinger dextrin for having modified bioactive molecule
Reacted in biological solution, that is, obtain being fixed with the polyelectrolyte multilayer film modified surface of bioactive molecule.
3. method according to claim 1 or 2, it is characterised in that:Described bioactive molecule is biotin, mannose
Or arginine-glutamic acid-aspartic acid-valine polypeptide.
4. method according to claim 3, it is characterised in that:It is modified with the system of the β-cdderivatives of the biotin molecule
It is for process:β-CD by propargyl biotin and the modification of 7 azido groups are:β-CD-(N3)7, click-reaction is carried out, is made
β-the CD of biotin modification.
5. method according to claim 3, it is characterised in that:It is modified with the system of the β-cdderivatives of the mannose molecules
It is for process:β-CD by propargyl mannose and the modification of 7 azido groups are:β-CD-(N3)7, click-reaction is carried out, is made
β-the CD of mannose-modified.
6. method according to claim 3, it is characterised in that:It is modified with the arginine-glutamic acid-aspartic acid-figured silk fabrics
The preparation process of the β-cdderivatives of propylhomoserin peptide molecule is:Propargyl-arginine-glutamic acid-aspartic acid-valine is more
Peptide and the β-CD of 7 azido group modifications are:β-CD-(N3)7, click-reaction is carried out, arginine-glutamic acid-asparagus fern ammonia is made
Peptide modified β-the CD of acid-valine.
7. method according to claim 1 or 2, it is characterised in that:The amidized base material is monocrystalline silicon or glass, institute
The preparation process for stating amidized monocrystalline silicon piece or sheet glass is:Monocrystalline silicon piece or sheet glass are placed in the second of 3- aminopropyls-three
TMOS(APTES)Toluene solution in react a period of time, obtain the monocrystalline silicon or glass baseplate of surface amination.
8. method according to claim 1 or 2, it is characterised in that:The amidized base material is gold-plated monocrystalline silicon piece, institute
The preparation process for stating amidized gold-plated monocrystalline silicon piece is:Gold-plated monocrystalline silicon piece is placed in the aqueous solution of mercaptoethylamine hydrochloride
Reaction a period of time, obtain the gold-plated single crystal silicon substrate of surface amination.
9. method according to claim 1 or 2, it is characterised in that:The β-cdderivatives of bioactive molecule are modified
Solution be the aqueous solution, phosphate buffer solution or other can dissolve the solution of corresponding bioactive molecule.
10. method according to claim 2, it is characterised in that:Described is polymerized to Invertible ideal,
The chain-transferring agent is 2-(Phenyl formyl sulfenyl)Propionic acid;Described initiator is azodiisobutyronitrile, azo two different heptan
Nitrile, dibenzoyl peroxide, dicetyl peroxydicarbonate ethylhexyl, isopropyl benzene hydroperoxide, potassium peroxydisulfate-sulphite body
System or hydrogen peroxide-perferrite system.
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