A kind ofly be applied to strengthen preparation technology than the polystyrene microsphere of turbid reagent
Technical field
Field of polymer microsphere materials of the present invention particularly, relates to a kind of preparation technology than the polystyrene microsphere of turbid reagent that is applied to strengthen.
Background technology
The preparation of polystyrene microsphere and application facet development are very fast; Many new technologies not only on the basis of traditional letex polymerization and suspension polymerization, have been developed; Also perfect day by day on the performance of microballoon, kind; Progressively develop into can synthesize that single dispersion, particle diameter are controlled, variform, structure, high performance product; Be widely used in fields such as standard metering, food chemical industry, medicine and pharmacology, biotechnology, information engineering and microelectronics, particularly be applied in biomedical sector, significant to the research of clinical diagnosis, check, immunological technique, cytology etc.In the external diagnosis reagent industry, polystyrene microsphere is to strengthen one of important source material than turbid reagent, and the performance of microballoon has determined the performance of reagent.
Letex polymerization (emulsion polymerization) is a kind of compound method commonly used in the Polymer Synthesizing process, and is because it is with water as solvent, very favourable to environment.Under the effect of emulsifying agent and by means of mechanical stirring, make monomer in water, be dispersed into milk sap, the polyreaction of being undertaken by the initiator initiation.Developed decades though this closes the title method, because moity is more in synthetic, each material proportion is complicated; Really can be advantageously applied to now enhancing than the polystyrene microsphere of turbid reagent seldom, the microballoon that performance is more stable also mainly comes from external major company, and is expensive; Like Polymicrospheres; Bangslabs etc. cost an arm and a leg, and are that 300 RMB-600 RMB/g do not wait.And the polystyrene microsphere of many homemade producers exists difference between batch big, poor stability, problem such as application performance is bad.These problems of existing polystyrene microsphere also are that many domestic manufacturers do not strengthen than one of the research and development of turbid reagent and major reason of throughput.
Polystyrene microsphere uses the microballoon of offshore company will cause other raw material of producing reagent to increase as strengthening one of important source material than turbid reagent, and reagent cost raises.Simultaneously, the microballoon of offshore company a lot of problems also occurred in than the process of turbid reagent being applied to enhancing, and on the low side like easy cohesion and antibody linked efficient, the production efficiency of reagent is difficult to problems such as raising.
Summary of the invention
Technical problem to be solved by this invention provides a kind of preparation technology than the polystyrene microsphere of turbid reagent that is applied to strengthen.
The present invention solves the problems of the technologies described above the technical scheme that is adopted: a kind ofly be applied to strengthen the preparation technology than the polystyrene microsphere of turbid reagent; Reaction system comprises outer water, polymerization single polymerization monomer and function monomer, and the component of said outer water and content are: sodium lauryl sulphate 0.1-2g, polyethylene glycol 6000 2-16g, sodium-chlor 0.1-3g, purified water 400-600mL; The component of polymerization single polymerization monomer and content are: vinylbenzene 50-100mL, Vinylstyrene 0.5-1.0 mL; The component of function monomer and content are: ethyl propenoate 2-16mL, boric acid borate buffer solution 10-60mL; This preparation technology comprises the steps:
(1) configuration of outer water: accurately measure purified water according to the content ratio of outer water and place dissolution vessel, accurately take by weighing sodium lauryl sulphate, polyethylene glycol 6000 and sodium-chlor again in dissolution vessel, stirring and dissolving;
(2) purifying of polymerization single polymerization monomer: by measuring vinylbenzene and Vinylstyrene containing of polymerization single polymerization monomer in separating funnel, add sodium hydroxide solution and shake up, remove the stopper in desolvating, draw unnecessary sodium hydroxide with purified water then;
(3) preparation of emulsion: stir the outer water for preparing and simultaneously the polymerization single polymerization monomer behind the purifying slowly is added dropwise to the outer aqueous phase for preparing, drip the mixing back and it is uniformly dispersed with ultrasonic instrument is ultrasonic;
(4) polyreaction: finely dispersed emulsion is poured in the reaction vessel; Stirring heating, treat that temperature rises to 65-85 ℃ after, add the initiator initiation reaction; After reaction 30-60min generates the polystyrene microsphere generation of no function group; Add function monomer, reacted 5.5-7.5 hour, obtain carboxylic polystyrene microsphere.
Particularly, the rotating speed that stirs in the said step (1) is 500-800rpm.
The quality percentage composition of sodium hydroxide solution is 5% in the said step (2).
The rotating speed that stirs in the said step (3) is 600rpm.
The power 40khz of ultrasonic instrument in the said step (3), ultrasonic to make its dispersive time be 10-30min.
Initiator in the said step (4) is an ammonium persulphate.
Function monomer divides 2 to 4 addings in the said step (4), and the amount that at every turn adds function monomer equates.Be about to divide n adding after function monomer evenly is divided into n part.N=2 or 3 or 4.
As adding mode preferably, function monomer divides 4 addings in the said step (4).
Said function monomer is that ethyl propenoate is scattered in the solution that the boric acid borate buffer solution constitutes.
The polystyrene microsphere that application performance is superior, it mainly receives composition of raw materials and two big factor affecting of technical process, and the core technology of technique scheme of the present invention is also just aspect these two.On original letex polymerization basis, increased the assistant for emulsifying agent polyoxyethylene glycol, make the microballoon of preparation Paint Gloss, size distribution is narrower; And added the adjusting material (sodium-chlor) of ionic strength, and be beneficial to charge balance, help the stability of whole emulsion system, the phenomenon of breakdown of emulsion can not appear.On polymer monomer, added linking agent (Vinylstyrene), make the polystyrene microsphere structure that obtains finer and close, molecular weight is higher.In the dispersion system of function monomer, added to novelty the boric acid borate buffer solution, regulated the acidity of whole system effectively, production technique is very stable.
Further; Acting in conjunction through temperature and stirring velocity; We can accurately control the size (deviation is no more than 10 nm) of institute's synthetic polystyrene microsphere; The mode that adds function monomer through needle tubing has solved the excessive problem of local acidity in the emulsion of function monomer adding back, and stability of emulsion is fine.
Among the above-mentioned preparation technology of the present invention, step (2) is the purifying of polymerization single polymerization monomer, according to the usage of trade and requirement; Vinylbenzene of producing and Vinylstyrene all can add stopper when preserving; Stopper can be selected Resorcinol HQ, and (have another name called quinhydrones, the most frequently used, price is low.The normal temperature effect is better; The heating cure effect is relatively poor) or para benzoquinone PBQ (under anoxia condition, still can play a role; The etherification procedure color that is applicable to nitrogen or other protection of inert gas is yellow; Influential to color of resin) or toluhydroquinone THQ (effective, be used for the production of high reactivity unsaturated polyester resin, be usually used in gel coating resin, SMC resin.These article solvability is good, and the high temperature polymerization inhibition effect is good), for fear of the influence of stopper to technology of the present invention; It is that 5% sodium hydroxide solution is removed stopper that the present invention adopts massfraction; Certainly, also can be as the case may be, the content of sodium hydroxide in the adjustment sodium hydroxide solution.Ultrasonic instrument in the step (3) can select for use promotion commonly used such as ultrasonator to dissolve finely dispersed ultrasonic device.
Compared with prior art, the invention has the beneficial effects as follows:
1, the polystyrene microsphere that adopts preparation technology of the present invention to produce, cost is 1% of offshore company's microballoon price.
2, the polystyrene microsphere that adopts preparation technology of the present invention to produce is with short production cycle, 6 hours only consuming time of a complete set of production technique.
3, adopt polystyrene microsphere that preparation technology of the present invention produces on using and superior, anti-freezing collection effect is that tens times of offshore company's microballoon and the cross-linking efficiency of antibody have improved 50%.
4, behind the polystyrene microsphere that employing preparation technology of the present invention produces, enhancing is to use 2 times of offshore company's microballoon than turbid reagent production efficiency.
5, adopt the polystyrene microsphere that preparation technology of the present invention produces after, strengthen than the cost of turbid reagent and descended 40% when using offshore company's microballoon.
6, the polystyrene microsphere that adopts preparation technology of the present invention to produce can reach the requirement that a kind of microballoon satisfies a plurality of projects simultaneously, and a ball is used more.
Description of drawings
Fig. 1 is a synthesis process flow diagram of the present invention;
Fig. 2 is the experimental result picture of polystyrene microsphere in the application of a1-MG mensuration test kit of instance 1 preparation;
Fig. 3 is the experimental result picture of polystyrene microsphere in the application of RBP mensuration test kit of instance 1 preparation;
Fig. 4 is the experimental result picture of polystyrene microsphere in the application of bladder chalone C determining reagent kit of instance 2 preparations;
Fig. 5 is the experimental result picture of polystyrene microsphere in the application of B2-MG mensuration test kit of instance 2 preparations;
Fig. 6 is the experimental result picture of polystyrene microsphere in the application of myohaemoglobin mensuration test kit of instance 3 preparations.
Embodiment
Below in conjunction with embodiment the present invention is made further detailed description, but embodiment of the present invention is not limited only to following embodiment.
Being applied to of present embodiment strengthens among the preparation technology than the polystyrene microsphere of turbid reagent, and core technology is embodied in composition of raw materials and two aspects of technical process.
The composition of raw materials material proportion is following:
Outer water: sodium lauryl sulphate (SDS) 0.1-2 g; Polyoxyethylene glycol (PEG-6000), promptly molecular weight is 6000 polyoxyethylene glycol 2-16 g; Sodium-chlor (NaCl) 0.1-3 g; Purified water (H
2O) 400-600 mL.
Polymerization single polymerization monomer: vinylbenzene (St) 50-100 mL; Vinylstyrene (DVB) 0.5-1.0 mL.
Function monomer: ethyl propenoate 2-16 mL, boric acid borate buffer solution 10-60 mL.
Said ratio as the present invention's prescription can zoom in or out according to its ratio geometric ratio.The reaction vessel of its reaction process and the specification of relevant device, the adjustment and the design that also adapt according to how much making of reactant.
The concrete prescription of present embodiment is as shown in table 1:
Table 1
Technical process comprises the steps:
(1) preparation of outer water
Accurately measure an amount of purified water in beaker according to the ratio of formula table, accurately take by weighing sodium lauryl sulphate (SDS), polyoxyethylene glycol (PEG-6000) and sodium-chlor again in beaker, 500-800rpm rotating speed stirring and dissolving.
(2) purifying of polymerization single polymerization monomer
Measure vinylbenzene and Vinylstyrene in proportion in separating funnel, add certain density sodium hydroxide and shake up, remove the stopper in desolvating.Draw unnecessary sodium hydroxide with purified water at last.
(3) preparation of emulsion
The polymerization single polymerization monomer good purifying slowly is added dropwise to the outer aqueous phase for preparing under the water 600rpm rotating speed outside.Mixing the back is uniformly dispersed it with ultrasonic instrument ultrasonic (power 40khz) 10-30min.
(4) polyreaction
Pour scattered emulsion in the specified reaction vessel into; Stirring heating, treat that temperature rises to assigned temperature after, add initiator ammonium persulfate and cause and react; After the polystyrene microsphere of no function group generates after reaction for some time; Add function monomer (ethyl propenoate) solution (adding respectively for 1 to 4 time by a certain percentage) for preparing in advance, be reacted to the scheduled time (6-8 hour), promptly generate carboxylic polystyrene microsphere.
Function monomer is that ethyl propenoate is scattered in the solution that the boric acid borate buffer solution constitutes.
Adopt above-mentioned prescription and synthesis technique, reacted material is measured through laser particle size analyzer and potentiometric titrator, and product is a carboxylic polystyrene microsphere.
In the table 1; Temperature in the synthesis technologic parameter is the temperature that rises to reaction in the step (4); Stirring velocity is the rotating speed of stirring and dissolving in the step (1); Cost is according to the prescription of present embodiment and technical process, through the input of material with finally obtain the production cost of every gram carboxylic polystyrene microsphere that the amount of product carboxylic polystyrene microsphere calculates.Find that through overtesting under the identical situation of other test conditionss, its cost had tangible reduction with respect to once adding when the number of times of adding function monomer was 2-4 time.Dividing under the situation about adding for 4 times, with respect to 1 adding, its cost significantly reduces.
For prescription and the prepared carboxylic polystyrene microsphere of synthesis technique pressed in the foregoing description in the table 1, we carry out further experiment.
Table 2
According to the experimental result of table 2, carboxylic polystyrene microsphere is as a kind of raw material that is used to produce other reagent, and the carboxylic polystyrene microsphere cost of present embodiment is for external microballoon, and cost is merely 1% of offshore company's microballoon price.External microballoon in the table 2 does
PolymicrospheresMicroballoon.
PolymicrospheresMicroballoon is a kind of in the existing microballoon of offshore company.
In table 1, press component and the prepared carboxylic polystyrene microsphere of technology of embodiment 1-3 for present embodiment, carry out application experiment respectively, in the application experiment below; For the contrast experiment in the same table, adopt microballoon to prepare ratio, parameter and the method for reagent, except microballoon different; Other component is all identical with condition; And adopting microballoon to make compositions and methods is existing technology, and those skilled in the art adopt conventional reagent compounding process to realize.
These microballoons are as shown in the table (in following each table in the relevant experimental data of the application of preparation related reagent; All data are all measured through automatic clinical chemistry analyzer; Location parameter and measuring method are prior art, and those skilled in the art adopt conventional determination techniques to realize.
Table 3
Table 3 is that the carboxylic polystyrene microsphere of embodiment 1 preparation is measured the application in the test kit at a1-MG; According to the mensuration result of table 3 and shown in Figure 2; Experimental result shows; The a1-MG that the reagent that adopts embodiment 1 to prepare is researched and developed far above the CB096D microballoon of utilization polymicrospheres the absorbancy changing value of each calibration object concentration determination measures test kit; When being 14 mg/L like calibration object concentration; The absorbancy changing value that the a1-MG of the CB096D microballoon research and development of polymicrospheres measures test kit is 602 units, and adopts the pairing absorbancy changing value of reagent of embodiment 1 preparation that 1004 units are arranged fully, and the a1-MG that response intensity is researched and developed than the CB096D microballoon of polymicrospheres measures test kit and surpassed 40%; Can see among Fig. 2 that the absorbancy of response curve on each calibration object concentration of the reagent of embodiment 1 preparation all is higher than the a1-MG mensuration test kit of the CB096D microballoon research and development of polymicrospheres; Therefore we have drawn as drawing a conclusion: the a1-MG of the CB096D microballoon research and development of utilization polymicrospheres measures test kit, and response intensity is low, can not solve microballoon agglutinative problem simultaneously; Microballoon aggegation rate surpasses 20%, and stability has only tens days.Utilization embodiment 1, we can see the test kit response intensity the made CB096D microballoon considerably beyond polymicrospheres, and the test kit cost directly descends 30%, the while has solved microballoon agglutinative problem fully, and is stable more than 1 year.
Table 4
Table 4 is that the carboxylic polystyrene microsphere of embodiment 1 preparation is measured the application in the test kit at RBP; Adopt the reagent of embodiment 1 preparation that the absorbancy changing value of each calibration object concentration determination is measured test kit far above the RBP of the CB091E microballoon research and development of utilization polymicrospheres; When being 11 mg/L like calibration object concentration; The absorbancy changing value that the RBP of the CB091E microballoon research and development of polymicrospheres is measured test kit is 750 units; And adopt the pairing absorbancy changing value of reagent of embodiment 1 preparation that 1302 units are arranged fully; Response intensity is measured test kit than the RBP of the CB091E microballoon research and development of polymicrospheres and has been surpassed 70%; Can see among Fig. 3 that the absorbancy of response curve on each calibration object concentration of the reagent of embodiment 1 preparation all is higher than the RBP mensuration test kit of the CB091E microballoon research and development of polymicrospheres, referring to shown in Figure 3, experiment shows; The RBP of the microballoon research and development of utilization embodiment 1 is measured test kit, the CB091E microballoon of the far ultra polymicrospheres of response intensity.Behind the microballoon of application implementation example 1; When certain auxiliary material add-on is 5 times of CB091E microballoon of polymicrospheres; Reagent still can be avoided the microballoon aggegation, and the anti-freezing effect that reagent is described is its 5 times at least, and the microballoon of use embodiment 1 is with 25% of direct saving cost.Simultaneously, exactly because the superpower response intensity of the test kit that this microballoon is researched and developed, it is the test kit that a present domestic unique family can measure urine and blood preparation simultaneously that the RBP of our research and development is measured test kit.
Table 5
Table 5 is the application at bladder chalone C determining reagent kit of the polystyrene microsphere of instance 2 preparations; The bladder chalone C determining reagent kit that the reagent that adopts embodiment 2 to prepare is researched and developed far above the CB0104D microballoon of utilization polymicrospheres the absorbancy changing value of each calibration object concentration determination; When being 0.5 mg/L like calibration object concentration; The absorbancy changing value of the bladder chalone C determining reagent kit of the CB0104D microballoon research and development of polymicrospheres is 164 units; And adopt the pairing absorbancy changing value of reagent of embodiment 2 preparations that 327.5 units are arranged fully, and response intensity is 2 times of bladder chalone C determining reagent kit of the CB0104D microballoon research and development of polymicrospheres, the absorbancy of response curve on each calibration object concentration of reagent that can see embodiment 2 preparations among Fig. 5 is all far above the bladder chalone C determining reagent kit of the CB0104D microballoon research and development of polymicrospheres; Response intensity is high; Particularly the low side response intensity is high, helps the mensuration of urine specimen, and experiment shows; The bladder chalone C determining reagent kit of the microballoon research and development of utilization embodiment 2; Response intensity is far above the CB0104D microballoon of polymicrospheres, and embodiment 2 microballoons can reach to concentrate and produce (the reagent liquid concentrator of making 1 L can be diluted to 2-3 L) in addition, and (concentration is too high and the CB0104D microballoon of polymicrospheres can not concentrate production; Its microballoon can serious aggegation), so the production efficiency of embodiment 2 microballoons is far above its (be its 2-3 doubly); In addition, about 60% the raw material that embodiment 2 microballoons only need add the CB0104D microballoon of polymicrospheres just can reach identical response intensity with the reagent of the CB0104D microballoon research and development of polymicrospheres, and cost directly descends 40%.
Table 6
Table 6 is the polystyrene microsphere of instance 2 preparations is measured test kit at B2-MG application; The B2-MG that the reagent that adopts embodiment 2 to prepare is researched and developed far above the CB0130E microballoon of utilization polymicrospheres the absorbancy changing value of each calibration object concentration determination measures test kit; When being 1.5 mg/L like calibration object concentration; The absorbancy changing value that the B2-MG of the CB0130E microballoon research and development of polymicrospheres measures test kit is 397 units; And adopt the pairing absorbancy changing value of reagent of embodiment 2 preparations that 782 units are arranged fully; Response intensity is higher 1 times than the B2-MG mensuration test kit of the CB0130E microballoon research and development of polymicrospheres; Can see among Fig. 5 that the absorbancy of response curve on each calibration object concentration of the reagent of embodiment 2 preparation all measure test kit far above the B2-MG of the CB0130E microballoon research and development of polymicrospheres; Use the test kit of the microballoon research and development of instance 2 simultaneously, directly descend more than 30% at the cost aspect the raw material.
Can see from embodiment 1 and embodiment 2; Same a kind of microballoon can satisfy the requirement of 2 kinds of reagent simultaneously; And the performance of reagent will be got well much than the reagent that adopts the research and development of polymicrospheres microballoon; Simultaneously because the microballoon price of new Cheng Ziyan is merely 1% of polymicrospheres microballoon, this makes our cost of reagent generally descend more than 20% even has reached 40%.
Table 7
Table 7 is the polystyrene microsphere of instance 3 preparations is measured test kit at myohaemoglobin application; Adopt the reagent of embodiment 3 microballoons preparation that the absorbancy changing value of each calibration object concentration determination is measured test kit far above the myohaemoglobin of the CB0267D microballoon research and development of utilization polymicrospheres; When being 110 ng/L like calibration object concentration; The absorbancy changing value that the myohaemoglobin of the CB0267D microballoon research and development of polymicrospheres is measured test kit is 135 units; And adopt the pairing absorbancy changing value of reagent of embodiment 3 preparations that 439 units are arranged fully; It is high 3 times that response intensity is measured test kit than the myohaemoglobin of the CB0267D microballoon research and development of polymicrospheres; Can see among Fig. 6 embodiment 3 preparation reagent the absorbancy of response curve on each calibration object concentration all considerably beyond the myohaemoglobin of CB0267D microballoon research and development of polymicrospheres measure test kit; As the reagent of this trace detection of picture myohaemoglobin, the size of response intensity is reagent performance quality and important evaluating index thereof.Experiment shows that the myohaemoglobin of the microballoon research and development of utilization embodiment 3 is measured test kit, and response intensity is considerably beyond the CB0267D microballoon of polymicrospheres, reagent excellent property.