CN101551334A - Drug morphia molecular recognition sensitivity chip of optical sensor and producing method thereof - Google Patents
Drug morphia molecular recognition sensitivity chip of optical sensor and producing method thereof Download PDFInfo
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- CN101551334A CN101551334A CNA2009101191645A CN200910119164A CN101551334A CN 101551334 A CN101551334 A CN 101551334A CN A2009101191645 A CNA2009101191645 A CN A2009101191645A CN 200910119164 A CN200910119164 A CN 200910119164A CN 101551334 A CN101551334 A CN 101551334A
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Abstract
The present invention belongs to a field for producing optical sensor chips, particularly relates to a drug morphia molecule recognition sensitivity chip and a producing method thereof. The drug morphia molecule recognition sensitivity chip of the invention is composed of two parts of a morphia molecular engram polymer film and a metallic film basal layer from the upper to the lower; wherein the metallic film base is that an optical microscopic glass is coated with a layer of metallic film through a vacuum vapor deposition method or a sputtering technique, and the morphia molecular engram polymer film is cross linked on the metallic film surface of the metallic film base through a chemical synthesis method. A stereo positive hole having multiple action sites and matching with the morphia molecule on the space and combining sites is formed in the polymer film structure, thereby it is capable of implementing a specificity and high-sensitivity recognition function of the drug morphia molecule. The molecule recognition sensitivity chip of the invention has a stable physical chemistry property, can be used for many times, is easy to be saved, has a simple production method, consumes few energy; and has a low production cost.
Description
Technical field
The invention belongs to the optical sensor chip preparation field, be specifically related to drug morphia molecular recognition sensitivity chip of a kind of optical sensor and preparation method thereof.
Background technology
Morphine (Morphine) is a kind of morphinane alkaloid that extracts from opium, is the effective constituent main in the opium, that content is maximum, and content is 4%～21%, average 10%.It is that German medical scholar in 1803 fills in elder brother (Seguin) and separates from opium.Then Germanization scholar Ze Erdina (P.W.A.sertiner) also successfully finished the extraction of morphine in 1806, and according to its name of using Greece " Morpheus " horse Fes (Morpheus) visually at animal and the experiment effect of self with its called after " morphine " (Morphine).History refining and that refine narcotics has been started in the appearance of morphine.
Morphine is a most important alkaloid in the opium, because of having strong analgesic activity, is widely used in clinical treatment.In smuggling, in the narco-trafficking, morphine is the primary raw material of synthetic heroin, thus by illegal production in large quantities, smuggle and peddle.In the process of beat drugs crime, the forensic science worker is devoted to various advanced persons' analytical technology means or method are applied to detection to morphine.The technological means or the method that are applied to the morphine detection at present are more, mainly contain chemical analysis method, immunological detection (IA), thin layer chromatography (TLC), vapor-phase chromatography (GC), high performance liquid chromatography (HPLC) and chromatogram/mass spectrometry analytic approach (GC-MS) etc.These methods all need sample is carried out pre-service, remove and disturb impurity, enrichment trace component to be measured, at sample composition complexity, extensive situation about detecting, said method needs technical skill personnel and extensive expensive instrument, be not suitable for the needs of scene of a crime fast detecting, and also there are problems such as the bad or specimen preparation excessive cycle of reappearance in some method.Under this background, domestic and international new detection technique and the sample pretreating method of forensic science worker active development.
Directly the morphine in the metabolin of mensuration biological fluid is one of challenge of forensic science worker always.People carry out all effort to seek easy, inexpensive, accurate, practical analytic system from different approach.In this respect, fruitful is biology sensor.Biology sensor is made up of recognition component and signal converter, recognition component is fixed on the surface of converter by rights, when testing molecule combines with recognition component, produce physics or chemical signal, converter with this conversion of signals become one can be quantitative output signal, realize The real time measure by monitoring output signal to testing molecule.The biomolecule that constitutes biology sensor has enzyme, antibody, microorganism, tissue even complete organ; Converter has electrode, field effect transistor, optical fiber, thermistor and piezoelectric crystal etc.Characteristics such as biology sensor is highly sensitive owing to it, selectivity good, response is fast, the sample demand is few, Miniaturized are subjected to extensive concern, are more and more used in forensic science, become the means of a kind of novelty that detects morphine.For example, Ri Ben people such as Go Sakai have studied success and utilize surface plasma resonance biosensor to pass through the detection of solution competition law to Morphine in Urine.The mBSA reaction that they at first fix the morphine antibody (macromolecule reactant) and the golden film substrate surface of series concentration is until saturated; Then with (making both reaction reach balance) after the morphine (analyte) of variable concentrations and certain density antibody preincubate a period of time, again with golden film substrate on fixing mBSA competition antibody.At the suprabasil signal of golden film, the concentration of micromolecule morphine can be detected with surface plasma resonance biosensor real time record macromolecular reaction thing, and the binding constant of analyte and macromolecular reaction thing in the solution can be tried to achieve by data processing.
But the defective that biomolecule is intrinsic is promptly had relatively high expectations to environment for use, is difficult to long preservation etc., biology sensor is run in actual applications much be difficult for the obstacle that overcomes.Simultaneously, biomolecule derives from biological living, because preparation and purifying are loaded down with trivial details, expensive, therefore, it also is a key factor of restriction biology sensor development that recognition component is difficult to.Obtaining cheap, stable recognition component, is one of key of further developing of biology sensor.
Molecular imprinting (Molecular Imprinting Technology, MIT) be the existing molecular recognition effect of simulating nature circle, as enzyme-to-substrate, antibody and antigen etc., preparation has the polymkeric substance of specific selectivity to a certain specific target molecules, be molecularly imprinted polymer (molecularly imprinted polymer, process MIP).At present, molecular imprinting has become the effective means of storage molecular information in the high molecular polymer, polymkeric substance is gone up at molecular level (level) predetermined substance is discerned.Molecularly imprinted polymer is very stable, than exacting terms as with an organic solvent or under the high-temperature condition, can not destroy its recognition capability yet.These advantages make molecularly imprinted polymer be suitable for doing the sensitive material of sensor.Wherein from application point, molecularly imprinted polymer can be divided into different types again, and molecular imprinted polymer membrane is developed the optimal selection of sensor Primary Component just.We with molecularly imprinted polymer as the senser element of sensitive material call the molecular engram sensor (Molecular Imprinting Sensor, MIS).The molecular engram sensor can optionally be discerned and in conjunction with microsphere, and by the variation output signal of signal converter according to the physical-chemical parameters in the cohesive process, and the power of signal is decided by the height of microsphere material concentration.Therefore, molecularly imprinted polymer is fixed on the recognition component of transducer face as sensor with the form of film, not only can overcome the shortcoming of biology sensor, and can improve the sensitivity and the detectability of sensor in long-time stability, abominable physicochemical environment (High Temperature High Pressure, strong acid and strong base) tolerance difference.1991, Mosbach etc. combine molecular imprinting and sensor first, MIP as recognition component, and has been applied for patent, the molecular engram sensor at herbicide, medicine, toxin, sugar, nucleic acid and amino acid whose derivant etc. has been arranged now.
At present, molecular imprinting is applied to the sensor morphine, also mainly is confined to the electrooptics sensor field.For molecular engram electrooptics sensor, the research of molecular engram optical sensor is later, but the type sensor is very attractive with its higher sensitivity.Optical sensor signals can be passed through Optical Fiber Transmission in addition, and loss is less, realizes remote the detection easily, and therefore, the molecular engram optical sensor has some unique advantages that are different from other sensor.Utilize the molecular engram optical sensor to detect morphine, still blank both at home and abroad at present, we do not retrieve the document or the patent report of relevant this respect as yet.But As time goes on going deep into of studying, people will appreciate that the value that this coupling technique is potential.The core and the key of this technology used and promoted in the preparation of molecular recognition sensitive chip just.
Summary of the invention
It is loaded down with trivial details, expensive to the objective of the invention is to overcome in the existing biology sensor that detects morphine molecular recognition sensitive chip preparation method, the shortcoming of tolerance difference aspect long-time stability, reusability, abominable physicochemical environment provides a kind of drug morphia molecular recognition sensitivity chip of optical sensor.
For achieving the above object, one of technical solution of the present invention provides a kind of drug morphia molecular recognition sensitivity chip of optical sensor, it is characterized in that: form by two parts, be followed successively by morphine molecular imprinted polymer membrane layer and metallic film base layer from top to bottom; Wherein, metallic film base is meant on the optical cover slide and plates the layer of metal film by vacuum vapor deposition method or sputtering method, and the morphine molecular imprinted polymer membrane is to utilize the metallic film surface of the method cross-linking of chemosynthesis in above-mentioned metallic film base, is used for optical sensor the morphine molecule is realized specificity, high sensitivity recognition function.
The drug morphia molecular recognition sensitivity chip of described a kind of optical sensor, its described metallic film are that metallic film is a kind of in golden film, silverskin, aluminium film or the copper film.
The drug morphia molecular recognition sensitivity chip of described a kind of optical sensor, the thickness of its described metallic film are 20～100nm.
The present invention also provides a kind of preparation method of drug morphia molecular recognition sensitivity chip of optical sensor, it is characterized in that: its concrete preparation process is as follows:
A) at first on the optical cover slide, plate the layer of metal film by vacuum vapor deposition method or sputtering method, with this as metallic film base;
B) one or both polymerization reaction monomers and morphine molecule are dissolved in the pore-foaming agent with certain proportion;
C) add crosslinking chemical and initiating agent with certain proportion again, logical nitrogen deoxygenation number minute after the ultrasonication;
D) peek is dripped by step b) and c) pre-polymer solution that is dissolved with the morphine molecule formed drips on the silanization microslide that is stained with support membrane, covers metallic film base;
E) bilayer made in step d) reaction sheet is put into closed reactor, under nitrogen protection, in uniform temperature heating stoichiometric number hour;
F) reaction after finishing separates microslide and metallic film base, can be inlaid with the functional polymer polymer film of morphine molecule at the surface-crosslinked last layer of the metallic film of metallic film base;
G) utilize eluant, eluent to remove to be embedded in morphine molecule in the functional polymer polymer film;
H) gained chip in the step g) is dried to weight under vacuum condition, obtains being used for the drug morphia molecular recognition sensitivity chip of optical sensor.
The preparation method of the drug morphia molecular recognition sensitivity chip of described a kind of optical sensor, polymerization reaction monomer described in its step b) adopts following one or both compound: acrylic acid, methacrylic acid, trifluoromethyl acrylate, methyl methacrylate, methylene-succinic acid, hydroxyethyl methylacrylate; Crosslinking chemical described in the step c) is selected from one of following compound: ethylene glycol dimethacrylate, N, N '-methylene diacrylamine, pentaerythritol triacrylate, tetramethylol methane tetraacrylate, trimethylol-propane trimethacrylate or divinylbenzene; Pore-foaming agent described in the step b) is following one or both compound: methylene chloride, methenyl choloride, methyl alcohol, acetonitrile, N, dinethylformamide, sulfone compound or heterocycle compound; Initiating agent described in the step b) is selected from one of following compound azoisobutyronitrile, ABVN, 2,2 '-azo-two (2, the 4-methyl pentane nitrile) or benzoyl peroxide;
The preparation method of the drug morphia molecular recognition sensitivity chip of described a kind of optical sensor, the consumption proportion of its described each reactant is as follows:
Described polymerization reaction monomer is 2～10: 1 with the amount of substance ratio of described microsphere
Described crosslinking chemical is 4～20: 1 with the amount of substance ratio of described microsphere
Described crosslinking chemical is 1～10: 1 with the amount of substance ratio of described polymerization reaction monomer;
Described initiating agent is 0.06～0.15: 1 with the amount of substance ratio of described polymerization reaction monomer
The preparation method of the drug morphia molecular recognition sensitivity chip of described a kind of optical sensor, ultrasonic time is 5～10min in its described step c), the logical nitrogen deoxygenation time is 5～10min; The heating temperature of reaction is 55～70 ℃ in the described step d), and the reaction time is 3.5～24 hours.
The preparation method of the drug morphia molecular recognition sensitivity chip of described a kind of optical sensor, the eluant, eluent described in its step g) is the mixed liquor of organic solvent and acid or organic solvent and water, sour mixed liquor.Described organic solvent is methyl alcohol or acetonitrile, and described acid is acetate, and acid with the volume of organic solvent ratio be 1: 1～50 or water, acid with the volume of organic solvent ratio be 1: 1～10: 1～500.
The preparation method of the drug morphia molecular recognition sensitivity chip of described a kind of optical sensor, the silanization microslide that is stained with support membrane described in its described step d) adopts following method to obtain: with chromic acid lotion, redistilled water and ethanol microslide is not cleaned repeatedly until having obviously at first successively and pollute; Place Piranha solution afterwards, i.e. H
2SO
4: H
2O
2(3: 1, in 50 ℃ of heating one hour, use distilled water, ethanol drip washing more successively, and dry up in mixed solution V/V) with nitrogen; Soaked overnight in the ethanolic solution of 50mM trimethyl chlorosilane makes it silanization at last; Before each the use, at first use ethanol drip washing silanization microslide, and dry up with nitrogen, then the surface that film tightly is bonded at the silanization microslide of sealing of getting well with drawing, mark a square white space with blade at the zone line that seals film again, the film that seals residual on the microslide is support membrane, obtains being stained with the silanization microslide of support membrane.
Beneficial effect of the present invention: the drug morphia molecular recognition sensitivity chip of a kind of optical sensor provided by the present invention has utilized molecular imprinting, compares with traditional bio-sensing chip, has following outstanding advantage:
(1) not only the target molecule morphine is had extraordinary compatibility and selectivity, selectivity is strong, and closely similar with natural acceptor molecule;
(2) physicochemical property are stable, can resists very strong mechanical effect, and high temperature resistant, high pressure, acid, alkali and organic solvent are difficultly destroyed by biodegradation, are better than natural biological acceptor molecule aspect a lot.
(3) preparation method is simple, and power consumption is few, and the reaction time is short, and is totally pollution-free, is easy to promote;
(4) more biological golden film substrate is easy to preserve and use;
(5) can be repeatedly used, can stable for extended periods of time.
Description of drawings
Fig. 1 is preparation method's synoptic diagram of imprinted polymer rete of morphine branch of the drug morphia molecular recognition sensitivity chip of a kind of optical sensor of the present invention;
Fig. 2 is the synoptic diagram of the drug morphia molecular recognition sensitivity chip of a kind of optical sensor of the present invention;
Fig. 3 is the response spectrogram of drug morphia molecular recognition sensitivity chip on surface plasma resonance sensor among the embodiment 1;
Fig. 4 is the response spectrogram of drug morphia molecular recognition sensitivity chip on surface plasma resonance sensor among the embodiment 2;
Fig. 5 is the response spectrogram of drug morphia molecular recognition sensitivity chip on surface plasma resonance sensor among the embodiment 3;
Fig. 6 is the response spectrogram of drug morphia molecular recognition sensitivity chip on surface plasma resonance sensor among the embodiment 4;
Fig. 7 is the response spectrogram of drug morphia molecular recognition sensitivity chip on surface plasma resonance sensor among the embodiment 5.
Among the figure, 1-metallic film, 2-optical cover slide, 3-support membrane, 4-silanization microslide, 5-are dissolved with pre-polymer solution, the 6-morphine molecular imprinted polymer membrane of morphine.
Specific embodiment
The invention will be further described below in conjunction with drawings and Examples.
A kind of drug morphia molecular recognition sensitivity chip of optical sensor is made up of two parts, is followed successively by morphine molecular imprinted polymer membrane layer and metallic film base layer from top to bottom; Wherein, metallic film base is meant on optical cover slide 2 and plates layer of metal film 1 by vacuum vapor deposition method or sputtering method, and morphine molecular imprinted polymer membrane 6 is to utilize the metallic film surface of the method cross-linking of chemosynthesis in above-mentioned metallic film base, is used for optical sensor the morphine molecule is realized specificity, high sensitivity recognition function.
Embodiment 1
At first on the optical cover slide, plate the thick golden film of one deck 47nm by vacuum vapor deposition method, with this as golden film substrate.Accurately take by weighing microsphere morphine 0.0143 (0.05mmol) and polymerization reaction monomer methacrylic acid 0.0172g (0.2mmol), be dissolved in the 3.0mL dimethyl sulfoxide (DMSO), behind the ultrasonic hydrotropy 5min; In above-mentioned mixed liquor, add the crosslinking chemical ethylene glycol dimethacrylate of 0.0496g (0.25mmol) and the initiating agent azoisobutyronitrile of 0.0030g again, behind the ultrasonication 5min, logical nitrogen deoxygenation 5mim; Peek is dripped drips of solution and is added on the silanization microslide that is stained with support membrane, covers golden film substrate, and with clip the two is clamped; With above-mentioned make bilayer reaction sheet put into closed reactor, under nitrogen protection, in 60 ℃ of water-baths, added thermal response 24 hours; Reaction after finishing separates microslide and golden film substrate, can be inlaid with the functional polymer polymer film of morphine molecule at the crosslinked last layer of golden film substrate surface.Utilize volume ratio be the mixed liquor of 4: 1: 1 methyl alcohol, acetate and water remove the functional polymer polymer film in the morphine molecule.After wash-out finishes, the gained chip is dried to weight under vacuum condition, obtains being used for the drug morphia molecular recognition sensitivity chip of optical sensor at last.
At first on the optical cover slide, plate the thick golden film of one deck 47nm by vacuum vapor deposition method, with this as golden film substrate.The microsphere morphine of 0.0077g (0.025mmol) is joined bottom in the 5ml round-bottomed flask, and be placed in 115 ℃ the oil bath and heat 15min, then to wherein adding methacrylic acid 0.0086g (0.1mmol), after treating the two formation oily mater, add the crosslinking chemical ethylene glycol dimethacrylate of 0.0496g (0.25mmol), the acetonitrile of 1.0ml and the initiating agent azoisobutyronitrile of 0.0030g more successively, behind the ultrasonication 5min, logical nitrogen deoxygenation 10mim; Peek is dripped drips of solution and is added on the silanization microslide that is stained with support membrane, covers golden film substrate, and with clip the two is clamped; With above-mentioned make bilayer reaction sheet put into closed reactor, under nitrogen protection, in 65 ℃ of water-baths, added thermal response 5 hours; Reaction after finishing separates microslide and golden film substrate, can be inlaid with the functional polymer polymer film of morphine molecule at the crosslinked last layer of golden film substrate surface; Utilizing volume ratio is that the mixed liquor of 9: 1 acetonitrile and acetate is removed the morphine molecule in the functional polymer polymer film.After wash-out finishes, the gained chip is dried to weight under vacuum condition, obtains being used for the drug morphia molecular recognition sensitivity chip of optical sensor at last.The response curve of prepared drug morphia molecular recognition sensitivity chip on surface plasma resonance sensor as shown in Figure 4.
At first on the optical cover slide, plate the thick golden film of one deck 47nm by vacuum vapor deposition method, with this as golden film substrate.Accurately take by weighing microsphere morphine 0.0143 (0.05mmol) and polymerization reaction monomer methacrylic acid 0.0172g (0.2mmol), be dissolved in volume ratio and be in 7: 3 the acetonitrile and dimethyl sulfoxide (DMSO) mixed solvent, behind the ultrasonic hydrotropy 5min; In above-mentioned mixed liquor, add the crosslinking chemical ethylene glycol dimethacrylate of 0.0793g (0..4mmol) and the initiating agent azoisobutyronitrile of 0.0050g again, behind the ultrasonication 5min, logical nitrogen deoxygenation 10mim; Peek is dripped drips of solution and is added on the silanization microslide that is stained with support membrane, covers golden film substrate, and with clip the two is clamped; With above-mentioned make bilayer reaction sheet put into closed reactor, under nitrogen protection, in 65 ℃ of water-baths, added thermal response 24 hours; Reaction after finishing separates microslide and golden film substrate, can be inlaid with the functional polymer polymer film of morphine molecule at the crosslinked last layer of golden film substrate surface; Utilizing volume ratio is that the mixed liquor of 8: 2 methyl alcohol and acetate is removed the morphine molecule in the functional polymer polymer film.After wash-out finishes, the gained chip is dried to weight under vacuum condition, obtains being used for the drug morphia molecular recognition sensitivity chip of optical sensor at last.The response curve of prepared drug morphia molecular recognition sensitivity chip on surface plasma resonance sensor as shown in Figure 5.
At first on the optical cover slide, plate the thick golden film of one deck 47nm by vacuum vapor deposition method, with this as golden film substrate.Accurately take by weighing microsphere morphine 0.0214g (0.075mmol) and polymerization reaction monomer methacrylic acid 0.0258g (0.3mmol), be dissolved in 4.0mLN, in the dinethylformamide, behind the ultrasonic hydrotropy 5min; In above-mentioned mixed liquor, add the crosslinking chemical ethylene glycol dimethacrylate of 0.1189g (0.6mmol) and the initiating agent azoisobutyronitrile of 0.0040g again, behind the ultrasonication 5min, logical nitrogen deoxygenation 10mim; Peek is dripped drips of solution and is added on the silanization microslide that is stained with support membrane, covers golden film substrate, and with clip the two is clamped; With above-mentioned make bilayer reaction sheet put into closed reactor, under nitrogen protection, in 60-65 ℃ of water-bath, added thermal response 5 hours; Reaction after finishing separates microslide and golden film substrate, can be inlaid with the functional polymer polymer film of morphine molecule at the crosslinked last layer of golden film substrate surface; Utilizing volume ratio is that the mixed liquor of 9: 1 methyl alcohol and acetate is removed the morphine molecule in the functional polymer polymer film.After wash-out finishes, the gained chip is dried to weight under vacuum condition, obtains being used for the drug morphia molecular recognition sensitivity chip of optical sensor at last.The response curve of prepared drug morphia molecular recognition sensitivity chip on surface plasma resonance sensor as shown in Figure 6.
At first on the optical cover slide, plate the thick golden film of one deck 47nm by vacuum vapor deposition method, with this as golden film substrate.Accurately take by weighing microsphere morphine 0.0143 (0.05mmol) and polymerization reaction monomer methacrylic acid 0.0172g (0.2mmol), be dissolved in the 3.0mL methyl alcohol, behind the ultrasonic hydrotropy 5min; In above-mentioned mixed liquor, add the crosslinking chemical ethylene glycol dimethacrylate of 0.0496g (0.25mmol) and the initiating agent azoisobutyronitrile of 0.0030g again, behind the ultrasonication 5min, logical nitrogen deoxygenation 5mim; Peek is dripped drips of solution and is added on the silanization microslide that is stained with support membrane, covers golden film substrate, and with clip the two is clamped; With above-mentioned make bilayer reaction sheet put into closed reactor, under nitrogen protection, in 60 ℃ of water-baths, added thermal response 3.5 hours; Reaction after finishing separates microslide and golden film substrate, can be inlaid with the functional polymer polymer film of morphine molecule at the crosslinked last layer of golden film substrate surface; Utilizing volume ratio is that the mixed liquor of 7: 3 methyl alcohol and acetate is removed the morphine molecule in the functional polymer polymer film.After wash-out finishes, the gained chip is dried to weight under vacuum condition, obtains being used for the drug morphia molecular recognition sensitivity chip of optical sensor at last.The response curve of prepared drug morphia molecular recognition sensitivity chip on surface plasma resonance sensor as shown in Figure 7.
Claims (9)
1. the drug morphia molecular recognition sensitivity chip of an optical sensor is characterized in that: comprise two parts, be followed successively by morphine molecular imprinted polymer membrane layer and metallic film base layer from top to bottom; Wherein, metallic film base is meant at optical cover slide (2) and upward plates layer of metal film (1) by vacuum vapor deposition method or sputtering method, and morphine molecular imprinted polymer membrane (6) is to utilize the metallic film surface of the method cross-linking of chemosynthesis in above-mentioned metallic film base, is used for optical sensor the morphine molecule is realized specificity, high sensitivity recognition function.
2. the drug morphia molecular recognition sensitivity chip of a kind of optical sensor as claimed in claim 1 is characterized in that: described metallic film is a kind of in golden film, silverskin, aluminium film or the copper film.
3. the drug morphia molecular recognition sensitivity chip of a kind of optical sensor as claimed in claim 1, it is characterized in that: the thickness of described metallic film is 20～100nm.
4. the preparation method of the drug morphia molecular recognition sensitivity chip of an optical sensor, it is characterized in that: its concrete preparation process is as follows:
A) at first on the optical cover slide, plate the layer of metal film by vacuum vapor deposition method or sputtering method, with this as metallic film base;
B) one or both polymerization reaction monomers and morphine molecule are dissolved in the pore-foaming agent with certain proportion;
C) add crosslinking chemical and initiating agent with certain proportion again, logical nitrogen deoxygenation number minute after the ultrasonication;
D) peek is dripped by step b) and c) pre-polymer solution that is dissolved with the morphine molecule (5) formed drips on the silanization microslide (4) that is stained with support membrane (3), covers metallic film base;
E) bilayer made in step d) reaction sheet is put into closed reactor, under nitrogen protection, in uniform temperature heating stoichiometric number hour;
F) reaction after finishing separates microslide and metallic film base, can be inlaid with the functional polymer polymer film of morphine molecule at the surface-crosslinked last layer of the metallic film of metallic film base;
G) utilize eluant, eluent to remove to be embedded in morphine molecule in the functional polymer polymer film;
H) gained chip in the step g) is dried to weight under vacuum condition, obtains being used for the drug morphia molecular recognition sensitivity chip of optical sensor.
5. the preparation method of the drug morphia molecular recognition sensitivity chip of a kind of optical sensor according to claim 4 is characterized in that: the polymerization reaction monomer described in the step b) adopts following one or both compound: acrylic acid, methacrylic acid, trifluoromethyl acrylate, methyl methacrylate, methylene-succinic acid, hydroxyethyl methylacrylate; Crosslinking chemical described in the step c) is selected from one of following compound: ethylene glycol dimethacrylate, N, N '-methylene diacrylamine, pentaerythritol triacrylate, tetramethylol methane tetraacrylate, trimethylol-propane trimethacrylate or divinylbenzene; Pore-foaming agent described in the step b) is following one or both compound: methylene chloride, methenyl choloride, methyl alcohol, acetonitrile, N, dinethylformamide, sulfone compound or heterocycle compound; Initiating agent described in the step b) is selected from one of following compound azoisobutyronitrile, ABVN, 2,2 '-azo-two (2, the 4-methyl pentane nitrile) or benzoyl peroxide.
6. according to the preparation method of the drug morphia molecular recognition sensitivity chip of claim 4 or 5 described a kind of optical sensors, it is characterized in that: the consumption proportion of each reactant is as follows:
Described polymerization reaction monomer is 2～10: 1 with the amount of substance ratio of described microsphere;
Described crosslinking chemical is 4～20: 1 with the amount of substance ratio of described microsphere;
Described crosslinking chemical is 1～10: 1 with the amount of substance ratio of described polymerization reaction monomer;
Described initiating agent is 0.06～0.15: 1 with the amount of substance ratio of described polymerization reaction monomer.
7. the preparation method of the drug morphia molecular recognition sensitivity chip of a kind of optical sensor according to claim 4, it is characterized in that: ultrasonic time is 5～10min in the described step c), the logical nitrogen deoxygenation time is 5～10min; The heating temperature of reaction is 55～70 ℃ in the described step d), and the reaction time is 3.5～24 hours.
8. the preparation method of the drug morphia molecular recognition sensitivity chip of a kind of optical sensor according to claim 4 is characterized in that: the eluant, eluent described in the step g) is the mixed liquor of organic solvent and acid or organic solvent and water, sour mixed liquor; Described organic solvent is methyl alcohol or acetonitrile, and described acid is acetate, and acid with the volume of organic solvent ratio be 1: 1～50 or water, acid with the volume of organic solvent ratio be 1: 1～10: 1～500.
9. the preparation method of the drug morphia molecular recognition sensitivity chip of a kind of optical sensor according to claim 4, it is characterized in that: the silanization microslide that is stained with support membrane described in the step d) adopts following method to obtain: with chromic acid lotion, redistilled water and ethanol microslide is not cleaned repeatedly until having obviously at first successively and pollute; Place Piranha solution afterwards, i.e. H
2SO
4: H
2O
2(3: 1, in 50 ℃ of heating one hour, use distilled water, ethanol drip washing more successively, and dry up in mixed solution V/V) with nitrogen; Soaked overnight in the ethanolic solution of 50mM trimethyl chlorosilane makes it silanization at last; Before each the use, at first use ethanol drip washing silanization microslide, and dry up with nitrogen, then the surface that film tightly is bonded at the silanization microslide of sealing of getting well with drawing, mark a square white space with blade at the zone line that seals film again, the film that seals residual on the microslide is support membrane, obtains being stained with the silanization microslide of support membrane.
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| CN1139810C (en) * | 1998-11-10 | 2004-02-25 | 长沙市精神病医院 | Method and test paper of smei-quantitative determination of morphine by monoclone antibody immune chromatography |
| US6593142B2 (en) * | 2000-04-10 | 2003-07-15 | The Johns Hopkins University | Polymeric food spoilage sensor |
| CN1228633C (en) * | 2000-06-02 | 2005-11-23 | 北京大学 | Establishment of anti-morphine single anti-cell strain and method for producing double-side morphine test paper |
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| CN103063649B (en) * | 2013-01-16 | 2014-11-19 | 哈尔滨工业大学 | Method for surface-enhanced Raman scattering spectrum detection by using silver-surface molecularly imprinted polymer |
| CN107722153A (en) * | 2017-11-13 | 2018-02-23 | 李辉 | A kind of Preparation method and use of more metal-complexing morphine trace high polymer new materials |
| CN107722153B (en) * | 2017-11-13 | 2019-11-29 | 骆雅雅 | A kind of Preparation method and use of more metal coordination morphine trace high polymer new materials |
| RU2693522C1 (en) * | 2018-07-09 | 2019-07-03 | Дмитрий Юрьевич Парфенов | Storage with increased protection against persons under the intoxication condition |
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