CN1302223A - Organic ion-selective membranes - Google Patents
Organic ion-selective membranes Download PDFInfo
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- CN1302223A CN1302223A CN 99806501 CN99806501A CN1302223A CN 1302223 A CN1302223 A CN 1302223A CN 99806501 CN99806501 CN 99806501 CN 99806501 A CN99806501 A CN 99806501A CN 1302223 A CN1302223 A CN 1302223A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/333—Ion-selective electrodes or membranes
- G01N27/3335—Ion-selective electrodes or membranes the membrane containing at least one organic component
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
- C08J5/20—Manufacture of shaped structures of ion-exchange resins
- C08J5/22—Films, membranes or diaphragms
- C08J5/2206—Films, membranes or diaphragms based on organic and/or inorganic macromolecular compounds
- C08J5/2275—Heterogeneous membranes
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2327/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers
- C08J2327/02—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers not modified by chemical after-treatment
- C08J2327/04—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers not modified by chemical after-treatment containing chlorine atoms
- C08J2327/08—Homopolymers or copolymers of vinylidene chloride
Abstract
The invention provides ion-selective membranes made without use of extraneous solvents, and methods of making such membranes. The membranes of the invention are less porous, more inert to water, have a longer shelf life, and are suitable for efficient manufacture in large quantities.
Description
Background of the present invention
1. the field of the invention
The present invention relates to ion selective membrane and preparation method thereof.Specifically relate to not utilize the modification of the polymer film that solvent makes.
2. the discussion of background technology
Ion selective membrane uses in many application, particularly uses in biology sensor and the analytical equipment.This film is separated test solution usually from reference solution, carry out the electrochemical measurement in the ion concentration difference of film both sides.The progress of theoretical research has at present been opened up prospect for improving this Device Testing limit significantly.But, chemistry and Engineering News Record (the 13rd page) report on November 24th, 1997, present commercial ion selective membrane has tangible restriction to total sensitivity.These films seriously limit their further features in the medium-term and long-term stability of the aqueous solution in addition.
Ion selective membrane is mainly used in the disposable field of biosensors.These film devices with these film manufacturings preferably have long storage period, low detectable limit and manufacturing on a large scale rapidly and effectively.But because utilization is traditional ion selective membrane, suction (suction) film is to storage period, and detectable limit and a large amount of manufacturing efficient have intrinsic restriction.
In a large amount of the measurement, owing to the tendency of the water absorption and swelling of film in the presence of water, so the stability of commercial ion selective membrane is a problem.Swelling not only makes the malformation of film, and has changed the permeability of film, and the component (multiple) of film is run off, and further changes the permeability of film and changes in the near zone ion concentration of this film or other chemical entities.The detectable limit of such deformation effect electrochemical measurement and accuracy.
Physics or chemical aspect unsettled film further limited the possibility of the biology sensor in the exploitation implantable.Utilize the device in the implantable to detect physiological conditions, for example during blood glucose value, if significantly distortion to take place when contacting with the aqueous solution or degrade be disadvantageous to the film in this device.Therefore, an urgent demand ion selective membrane will have long-term stability when contacting with the aqueous solution.
The ion selective membrane of prior art is by desired component being dissolved in the common solvent, then this mixture injection one suitable instrument being made into the shape of utilizing at electrode.There are many general issues in this technology.
For example, the solvent evaporation must be carried out under the condition of very strict control.If evaporation rate is too fast, film is formed sclerderm and at the many bubbles of subcutaneous generation.The bubble of Sheng Chenging is easy to separate with the surf zone of film like this, may produce the function through film.Certainly, this reduces with regard to the sensitivity that makes film, is created in complete otiose film in the electrode assembly most probably.
Another shortcoming of film casting method is, for the film for preparing the suitable depth that can process with instrument must repeat many times.The method of this repetition may increase the accumulation of bubble with each repeating step, therefore, has increased the large-area obstruction of film.
In many cases, find a kind of common solvent if not can not being exactly unusual difficulty, this is because be not that all components and additive combination with film helps being dissolved in a kind of solvent together.This is particular importance when the electrode sensor that automatic production edits in advance, can dispose, because in process of production, needed component and additive are not needed component and additive in the common employed film of laboratory ion selectivity sensor usually.
Suppose that various desired component always is not dissolved in a kind of solvent in ion selective membrane, so, the solution that will use solvent mixture to generate sometimes is from this solution film casting.But mixed solvent has produced other problem in evaporation step, particularly have under the situation of high boiling constant boiling mixture all the more so.In addition, because therefore the evaporation of solvent need may make the film cooling near the extraction energy of film.The reduction of this temperature can make the water vapour deposition, changes the surface of film and suppresses membrane material lower floor and the adhesion of the membrane portions of previous deposition.Before each new rete deposition, for fear of the viscosity and the concentration of component that change in the mixture, traditional casting film method also requires accurately to measure the volume of solvent mixture and stops solvent to evaporate from casting film solution.
Some improvement that film manufacturing method has been studied have proposed and some relevant problems of evaporation casting film.In a kind of so a kind of method, a glass ring adheres on a glass plate or the metallic plate.Then with in the polymer/solvent solution injection ring.This ring is topped and evaporate with slower speed with a big container.After the solvent evaporation, film is cut into disk-like shape with stamping machine.
In this method,, always which floor must not form film in because evaporation process is carried out slowlyer and more easy to control.But in this scheme, the restriction of the shortcoming that the advantage of a step casting film is evaporated slowly by solvent, the trouble of generation and the recuperable everywhere many useful film pans from process reduces.
The film that is utilized in the automatic production of sensor must be very even in batch process, long storage period also must be arranged and must produce by the mode that can be scheduled to.Owing to have many intrinsic problems preparing electrode film by solvent evaporation process, force the producer to produce film with less output.Make film with small capacity, not only reduced the waste product in the failure procedure, and reduced in the forming process of film production efficiency and production quantitative limitation.
Owing in solvent basement membrane prescription, between the different outputs very big variation is arranged, for example in the sensor production that can dispose, therefore more mass-produced attempts may be very invalid, can not produce and cost very high.Because these above-mentioned shortcomings, the solvent basement membrane is not very favourable to being assembled into the biology sensor that can dispose after making.
As a kind of yes-no decision, from a kind of film forming mixture of dissolving, make film on the spot.But this requires expensive equipment, and this equipment is wanted can a small amount of full-bodied solution of repeating dispersion, the deposition of anti-sealing subsequently, and the evaporation of control solvent makes the formation of bubble reduce to minimum, the long time of staying is arranged in this equipment and show manufacture process continuously.
Really, some difficulties of solvent base ion selective membrane and ineffectivity are provided with some strict restrictions to the device that adopts a large amount of manufacturings of this film to dispose.This is the mutability situation owing to product, and the film that the result makes is assembled into biosensor arrangement in the back manufacturing must prevent a large amount of losses of precious materials with small lot batch manufacture.To disposable medical devices, owing to produce suitable ineffectivity in the use of the film of making on the spot at equipment, this is real equally really.
When contacting with the aqueous solution, the problem of solvent base ion selective membrane inherent instability sometimes even more serious.This is because the membrane structure that the solvent evaporation stays the time is stayed the place of other scrambling in hole, passage back and the membrane structure.These artifacts of solvent evaporation make membrane structure distortion and electrochemical function distortion rapidly easily by water erosion.
So, must exploitation accurately install, up to the very short time that this device is used to measure, stop the film of the prior art in electrode assembly to contact with water.This is because the film of prior art generally all absorbs the moisture of significant quantity in the initial several seconds that contact with the aqueous solution.The absorption of water has changed geometry, composition and the electrochemical function of film.For example, when water moved through electrode film, the position of electromotive force also may be moved, and previous fixing additive and ion can begin diffusion equally in film.
The generation of the electromotive force of this phenomenon inhibition film both sides and the distortion of electromotive force numerical value in a short period of time, when the aqueous solution moves through film, also may cause electromotive force to lose fully.This is to make previous fixing active component produce mobile and diffusion in film because water infiltrates film, and the ion guide of therefore carrying them is sent a telegraph the formation of gesture.
If it is outer and disengage ion on the surface of film that these active ingredients move to film, the ion that the disengages outer local ion concentration of film that raise, the detectable limit of interfere with electrode.If active component is diffused into the reference solution side of film, the ion that before had been fixed in the film is used up, and the ability that produces electromotive force in the film both sides is lowered or is destroyed.Because the electrochemical properties of film just can change in several seconds process, so the measurement of membrane potential must promptly carry out by the utmost point, must relate to the approximation method and the extrapolation that make the mistake inevitably.
Therefore, the shortcoming of solvent base ion selective membrane comprises the ineffectivity of production and aspect the scrambling two of performance.The storage period of this intrinsic weak point, particularly all the more so in the presence of the moisture of any form, not best therefore to the disposable biology sensor that requires long storage period.Certainly, this film also is not suitable for using in the biosensor arrangement that implants fully, and this is owing to this reason aspect two of their reductions of physics and performance promptly and relevant with the implantation plastics usually biocompatibility issues when contacting with the aqueous solution.Therefore, be starved of the new method of making film and significantly reduced the absorption rate of water, simplified the modification ion selective membrane of making requirement and having improved biocompatibility widely.The invention discloses the film that demonstrates highly required character and its preparation method, this method has been carried out huge improvement in the prior art disclosed method.
General introduction of the present invention
The invention provides the method for producing ion selective membrane.In the method, the membrane component that comprises polymer and at least a additive mixes a kind of mixture that does not add solvent of generation mutually.Can make good ion selective membrane from this mixture.In this scheme of the present invention, polymer can be a vinyl chloride.Polymer also can polyvinyl chloride or the copolymer of vinyl chloride, for example, and the copolymer of vinyl acetate and/or vinyl alcohol.Equally, in this scheme of the present invention, additive can be a plasticizer.For example, suitable plasticizer can comprise following one or more, and they are: aromatic ether, aliphatic-aromatic ether, adipate ester, sebacate, phthalic acid ester, laurate, glutarate and phosphate.Additive also is the ion selectivity agent.
According to method of the present invention, membrane component can comprise more than one additive.For example, membrane component can comprise a kind of plasticizer and a kind of ion selectivity agent.Membrane component may further include additive, for example, and plasticizer modifier, active batching, ionic mobility reinforcing agent, heat stabilizer, light stabilizer, surface-active modifier, lipophilic agent and center fixed agent.
In the method for the invention, blend step can be included in the mixing of carrying out each component in the homogenizer.Can also comprise each component of heating.Manufacturing step in the method for the invention can comprise to be extruded mixture on the device of a suitable use film.Film also can be made by the injection moulding of mixture.In the enforcement of the inventive method, the present invention attempt makes each component reaction of biomolecule and film, a kind of key of formation between the film of the surface of biomolecule and film.The biomolecule that can react like this comprises, for example enzyme, acceptor class, steroids, nucleic acid class and antibody class.
Method of the present invention may further include the film surface is contacted with the water-containing materials that contains biomolecule, and whether generate has the two-layer ion selective membrane of solvent layer and water-bearing layer.In this scheme of the present invention, for example, biomolecule can be enzyme, acceptor class, steroids, nucleic acid class and antibody class.
In another program of the present invention, the invention provides the ion selective membrane of making by polymer and at least a additive that does not have solvent, wherein this film does not have solvent.For example, the polymer of film can be the copolymer of vinyl chloride, polyvinyl chloride or vinyl chloride, for example the copolymer of vinyl acetate and/or vinyl alcohol.Additive can be a kind of plasticizer.For example, useful plasticizer comprises aromatic ether, aliphatic-aromatic ether, adipate ester, sebacate, phthalic acid ester, laurate, glutarate and phosphate.Additive also can be the ion selectivity agent.Membrane component also can comprise one or more additive, for example, and a kind of plasticizer and ion selectivity agent.Membrane component may further include one or more additive, for example, and plasticizer modifier, active batching, ionic mobility reinforcing agent, heat stabilizer, light stabilizer, surface-active modifier, lipophilic agent and center fixed agent.
The curing mass loss of the ion selective membrane of this scheme of the present invention is less than 10%, or in certain embodiments less than 1%.The water absorption index of film is less than 0.5%, or in certain embodiments less than 0.1%.In some embodiments of the present invention, biomolecule can key to the surface of film.Useful biomolecule can comprise, for example enzyme, acceptor class, steroids, nucleic acid class and antibody class.Film also can have the surperficial contacted water-containing materials layer with film, and moisture material can comprise biomolecule.
In another program of the present invention, the improved biosensor arrangement that comprises an electrode is provided, wherein electrode has an ion selective membrane.In this scheme of the present invention, its improvement is that not have the ion selective membrane of solvent be to be made by polymer and at least a additive, and the Modified Membrane of wherein making does not have solvent.
Detailed description of the preferred embodiments
Film of the present invention does not use external solvent and makes.External solvent is a kind of solvent of interpolation, and it can improve the solubility of each component, and afterwards, this solvent was removed as the part of film forming.Because film of the present invention does not adopt external solvent, therefore do not require evaporation step.Because these films of making do not have the solvent evaporation step, so they demonstrate structure and the physical property different with the film of prior art.Most important character is degree and the speed that greatly reduces suction in these character.Because film of the present invention is difficult for suction, so they are not distorting rapidly aspect the electrochemical properties of structure, composition and worried prior art film.In addition, they are highly stable, and with during the aqueous solution contacts long time in demonstrate extraordinary reproducible electrochemical properties.In the application is the solution that described " aqueous solution " comprises any suitable water content, for example, and beverage, drug solution or suspension, culture or fermentation media, blood, blood plasma, urine, celiolymph, mucus secretion etc.
Except they and aqueous solution stability in contact, these films also have very long storage period, make the used device of these films and do not require special packing and think that diaphragm is not subjected to other measurement of moisture or moisture.And film of the present invention has the lower ion detection limit, more rapidly response, the mechanical strength of accurate and reproducible measurement result and Geng Gao is arranged in during long-time, for example can be under malleation or vacuum favourable use.Therefore, because film of the present invention has reduced the absorption of water widely, so they are very effective aspect fixing membrane component.That is to say, as described below, to compare with prior art film generally, the important additives in film is difficult for running off from film.
Film of the present invention is without the solvent manufacturing; They are by polymer, plasticizer and other unnecessary component being passed through to mix, making as generating the film forming mixture by mechanical mixture.For example, mechanical mixture can adopt well-known high speed blending machine or homogenizer in the plastics industry field.Component can add basic polymer separately or add basic polymer in the mode that makes up.These components can be plasticizer, heat stabilizer, UV absorbent, gamma-radiation stabilizing agent, antistatic additive, ion selectivity agent and other ligand, conductive agent, paraffin, hydrophober, flow and reduce agent etc.The problem relevant not with solvent, film of the present invention can be made desired any thickness in fact, not need the veneer of a series of control evaporation steps ought between produced film.
Do not have the mixture of the membrane component of solvent to modulate in advance, or directly add extruding machine or injection machine.The band of nascent membrane material can add high speed production unit easily.In this method, can produce the film of new feature or the mixture of new feature, so the manufacturing process of many selective membranes of known ion in advance in these mixtures.The thickness of film can be controlled with instrument or extrusion dies.What the film of Sheng Chaning can be a large amount of like this rolls, and produces chronically within several days or a few week and moves.Do not demonstrated the good character that surpasses above-mentioned prior art film owing to do not comprise solvent, film of the present invention.The per unit producing cost is very low, and a large amount of automated productions is very simple.
Should be pointed out that in many cases plasticizer can dissolve polymer.Therefore, some publications (for example, Suzuki, et al., Anal.chem.1989,61:382-384) in, itself is corruptly called solvent plasticizer.More correctly be that for the purposes of the present disclosure, this difference is to form between true solvent and plasticizer in film production.Be each component of dissolving film, use true solvent (external solvent), then, when film solidifies, remove out from film is all or part of.Removing generally of solvent finished by evaporation step, and this evaporation step has aforesaid shortcoming.Usually the example of employed true solvent comprises cyclohexanone, carrene, propene carbonate, the tetrahydrochysene furan food in one's mouth, toluene, first alcohol and water in the solvent based polyalcohol film of prior art.The film that the present invention makes does not add these or any external solvent, and very anti-and water or moisture solution contact the degraded that causes.
Opposite with true solvent, plasticizer also can be used for the dissolving film component, and still, it still is the part of film, does not require any evaporation step, does not also produce the structure product of evaporation step.In the solvent evaporating course, the solvent basement membrane solution of casting film forming will lose tangible quality, further form this difference.But in manufacture process, using does not have the mixture produced film of solvent not have tangible mass loss.Certainly, it is some shortcomings that the solvent evaporation is produced that the specific mass weight losses will obtain many, for example the porosity of malformation and film, in the film solidification process deposition, the vaporous parameter of water accurate control and/or utilize evaporation step to produce the long-term delay relevant and the shut-down of equipment with curing.
Film of the present invention, solvent-free, allow to improve widely throughput rate, control reduces significantly in the environment of the environment of mutability such as humidity mutability, avoided the difficulty of expensive expense relevant and environmental legislation and advantageously produced the film of water absorptivity less than prior art film water absorptivity with using and remove a large amount of organic solvents.Compare with the ion selective membrane of prior art, the water absorption of film of the present invention has reduced by 5 times, 10 times, 100 times or more.
The final densities of cured film provides the solvent base ion selective membrane of prior art and the difference between the solvent-free ion selective membrane of the present invention.Discuss as above-mentioned, the product that the solvent evaporation produces in film makes film produce the porosity of not wishing regularity.Otherwise product and atresia basically do not appear in solvent-free film.
In the filter membrane field, body hole calibration justice for " dead space " in the film with the membrane sample of known volume weigh and its basic polymer of density and existence and the gross density of additive are compared and are calculated.Concerning filter membrane, high body porosity is the condition of requirement.Otherwise ion selective membrane is desirable approaches zero body porosity one they is desirable non-porous.Difference between ideal and the reality is than expression (MDR) with film density.The MDR that the bubble or the solvent base ion selective membrane in hole are arranged is 80% or less than 80%, and the MDR of solvent-free film is preferably greater than 95% generally greater than 85%, more preferably greater than 99%.
Film of the present invention can contain a kind of polymer, normally the copolymer of polyvinyl chloride (PVC) or PVC; Plasticizer modifier; Active ingredient; The ionic mobility reinforcing agent; Heat stabilizer; Light stabilizer; The surface-active improver; The lipophilic agent; Center fixed agent and/or other component.PVC polymer or copolymer comprise basic, normal, high and super high molecular weight PVC.The copolymer of vinyl chloride such as vinyl chloride/vinyl acetate, vinyl chloride/vinyl alcohol and vinyl chloride/vinyl acetate/7 enols is also useful.Other suitable polymer blend is the polyvinyl chloride of carboxylation.
According to prescription, can use any several known plasticizers.The example of suitable plasticizer is an aromatic ether; Aliphatic-aromatic ether; Adipate ester, sebacate, phosphate, glutarate, phthalic acid ester and/or laurate; Aliphatic alcohol with long-chain.The limiting examples that agent modifier is made in plasticising is the paraffin hydrocarbon of halogenation, as the aliphatic alcohol of chlorinated paraffin wax hydrocarbon, long-chain, the nitrobenzene acetophenone of replacement.In film of the present invention, can comprise antibiosis (bacterium) element, liquid ion exchanger, neutral carrier, replacement amine, organic ammonium salt, crown ether-like, steroids, enzyme, antigen, antibody, dna binding factor and nucleic acid etc. together with the active ingredient that uses together.For example ion moves the wax class that reinforcing agent comprises stearate, long-chain alcohol and includes, but are not limited to paraffin hydrocarbon.The example of useful heat stabilizer is stearate, organo-metallic compound and chlorine acceptor.Light stabilizer can comprise two kinds of UV absorbent and photo-thermal transforming agents.The example of surface-active improver is cellulose triacetate, polyacrylamide, organic ammonium salt etc.
Active ingredient can not all be listed too much, has listed several useful especially ion selectivity agent in table 1.Those skilled in the art thinks, outside the agent of deionization selectivity, other active ingredient according to the application of specific (special) requirements and the character of film, can be selected and uses in film of the present invention, to obtain the film of best-of-breed functionality.
The example of table 1 ion selectivity agent
| Ion or other (quilt) analyte | Selectivity agent (multiple) |
| Ammonium | Nonactin |
| Calcium | Calcimycin (N, N, N ', N '-Fourth Ring hexyl-3-oxygen pentane diamides (-)-(R, R)-N, N '-[two (11-(carbethoxyl group) undecyl)]-N, N '-4,5-tetramethyl-3,6-dioxy octane-diamides N, N-dicyclohexyl-N ', N '-octacosyl-3-oxygen pentane diamides is two, and [4-(1,1,3, the 3-tetramethyl butyl) phenyl] synthos |
| Carbonate | Heptyl-4-trifluoroacetyl group benzoate 1-(dodecyl sulfonyl)-4-trifluoroacetyl group benzene N-dodecyl-4-trifluoroacetyl group antifebrin 4-butyl-α; α, α-trifluoroacetyl benzene |
| Chloride | Chlorination dotriacontyl first ammonium chlorination 5-10-15-20-tetraphenyl-21H, 23H-foretells quinoline manganese (III) 4,5-dimethyl-3,6-two hot oxygen-1,2 phenylenes-two (trifluoroacetic acid mercury) |
| Hydrogen | Tridodecylamine 4-nonadecyl pyridine octadecyl isonicotinic acid salt |
| Lithium | N, N, N ', N '-four isobutyl group-suitable-cyclohexane-1,2-dicarboxamide N, N-dicyclohexyl-N ', N '-diisobutyl-suitable-cyclohexane-1,2-dicarboxamide 5-butyl-5-ethyl-N, N, N ', N '-Fourth Ring hexyl 3,7-dioxy n-nonanoic acid diamides 12-crown-4; 1,4,7,10-four oxygen cyclododecanes 6,6-dibenzyl-14-is preced with-4 6-[2-(diethyl phosphorus oxygen)-ethyl]-6-dodecyl-14 hat-4 N, N, N ', N ', N "; N "-six cyclohexyl-4,4 ', 4 " phenylene-three-(3-oxygen butyramides) |
| Magnesium | N, N '-diheptyl-N, N '-dimethyl-1,4-butane diamides N, N " Ya Xinji-two (N '-heptyl-N '-methyl-methylmalonyl amine) N; N "-Ya Xinji-two (N '-heptyl-N '-methylmalonyl amine) N, N ', N " three [3-(heptyl methylamino)-3-oxygen propinyl]-8,8 '-imino-diacetic octyl amines |
| Potassium | Valinomycins two [(phendioxin 5-hat-5)-4 '-ylmethyl] pimelate 2-dodecyl-2-methyl isophthalic acid, 3-propane two bases-two-[N-(5 '-nitro (phendioxin 5-hat-5)-4 '-yl)-the ammonia formates] |
| Sodium | (N, N ', N " three heptyl-N; N '; N "-trimethyl-4,4 ', 4 " propylidyne-three-(3-oxygen butyramide) N; N '-dibenzyl N; N '-diphenyl-1; the inferior benzene dioxy of 2-diacetayl amide N; N; N ', N '-Fourth Ring hexyl-1, the inferior benzene dioxy of 2-diacetayl amide 4-octadecane acyl-oxygen ylmethyl-N, N, N ', N '-Fourth Ring hexyl-1, two [(12-crown-4) methyl] the dodecyl methyl malonate 4-tert-butyl calix[4 of 2-benzene dioxy diacetayl amide] aromatic hydrocarbons-tetraacetic acid tetraethyl ester decyl coban |
| Urine | Urease/ammonium ion |
| Glucose | Glucose oxidase/oxygen |
By with polymer, plasticizer and any other unnecessary component fusion hybrid films component.In some prescriptions, plasticizer also can be used as active ingredient, or active ingredient can be used as plasticizer.Therefore, the present invention attempt does not have the film of solvent by few to two kinds of component manufacturings, plans not had by the mixture manufacturing of various ingredients the film of solvent yet.
Mix and be simplified with the high speed blender or by Thermogelling effect and diffusion.Mixing can at room temperature be carried out, or selects different temperature according to the concrete combination of each component with character.For example, with wherein antibody or other protein adding film, the rising temperature can produce the problem of protein denitrogenation, therefore the temperature requirement restriction to using in film forming.When being chosen to film temperature other consideration comprise the work viscosity of the film mixture of requirement, when film forming on disposable device, the feasible value of other part temperatures of disposable device etc.
Can make film by extrusion molding and punching press, comprise on the spot directly extrusion molding on electrode assembly.Extrude by injection moulding or capillary, or squeeze on the spot on device, or in an independent process, also can make film.Other method of film forming for example comprises vacuum forming, vacuum forming, compression moulding, blowing and calendering.Film can be made any useful thickness in fact.
The present invention also comprises with the moisture above-mentioned film that does not have solvent of molecule coating, will contain hydrone and adhere to or be bonded in its surface.For example, catalyst (comprising enzyme) can work to change chemical substance on the surface of film, and described chemical substance is to enter and the product that directly detected by the electrode of device.In other schemes of the present invention, other molecule, structure or complex can work on the surface of film, or with strengthen or improve film or as the integral body of electrode assembly work.Useful molecule, structure or complex comprise hormone, antibody, antibiotic (life) element, nucleic acid, acceptor, in conjunction with albumen, pharmaceutical preparation, crystalline material etc.
For example, enzyme can be bonding as the urine enzyme or be adhered on the surface that does not have solvent membrane.This improvement makes membrane electrode can detect ionic species such as ammonium ion, also can the indirect detection nonionic as urine.That is to say that when the urine molecule in being tried solution contacted with the lip-deep urine enzyme that is fixed on the film that does not have solvent, enzymatic destroyed the ammonium ion that urine produces electrode detection.
The acceptor complex of band APT enzymatic activity equally also can be fixed on the surface that does not have solvent membrane to the phosphate ion sensitivity, the existence of measuring receptor ligand indirectly.When ligand connects acceptor, disengage phosphate ion from APT, these ions are by electrode detection simultaneously.Those skilled in the art think, by be fixed on the surface that does not have solvent membrane or this type of the analyte indirect detection that the solvable biomolecule of near surface helps with a wide range of applications.
There are many method preparations that the film of biomolecule or other needed molecule or structure is arranged in its surface.In a scheme of the present invention, there is not the film method as described in the present application of solvent to make.After film forming, the molecule of selection or the structure active group in polymer or copolymer chemically with the film keyed jointing.For example, amido can react with the chloro on polychloroethylene film in the coupling reaction that promotes as catalyst with silver ion.
In this scheme, generate covalent bond between the polymer of biomolecule and film forming.In another program, one or more that are selected from biomolecule are water-soluble, add the water-soluble poly mixture then and generate solution.The skim of this solution is with of the present invention prefabricated and do not have the film of solvent to contact.When the aqueous solution contacts with the film that does not have solvent or after the contact, the aqueous layer polymerization generates skim and is adhered on the film that does not have solvent, and this film comprises the thin layer of fixing biological molecules or other structure.
In another program of the present invention, make two films that separate.First kind of film is the film of extensively narrating among the application that does not have solvent.Second kind of film is the water base film that contains one or more water-soluble active ingredients such as biomolecule or other complex or structure.Though the rete of any useful thickness can put on the film that does not have solvent,, the thickness of water base film is generally the 1-100 micron.When water base film contacted with the film that does not have solvent, estimating was not having on the solvent membrane surface or near surface fixing biological molecules or other complex or structure.
In many this schemes, final result does not of the present inventionly have the film of solvent to become the film with the drainage that requires, and has fixed the molecule that requires water to carry out its function that requires simultaneously thereon yet.Therefore, the present invention is not limited only to contain the film that does not have solvent of one or more active ingredients, and is also included within its surface and uploads the film that does not have solvent of having held one or more desired water soluble molecules.Therefore, Gu Ding water soluble molecules changes into measurable material as enzyme catalyst with immeasurablel material.They also can play a part, and other is useful, for example eliminating that concentrates, do not need particle of required particle, the beginning etc. of biochemical path that causes needs and/or can measure product.
Embodiment
For the solvent basement membrane with prior art compares, prepare the representational film that does not have solvent.Test is selected from the membrane sample of calcium, potassium and ammonium.
Embodiment 1 calcium ion selective does not have solvent membrane
It is by following formulation: super high molecular weight PVC that calcium ion selective does not have solvent membrane, 100.00 parts; 2-nitrobenzophenone Octyl Ether, 250.00 parts; (-)-(R, R)-N, N '-(two (11-carbethoxyl group) undecyl)-N, N '-4,5-tetramethyl-3,6-dioxy octane diamides (calcium ion selective part), 7.5 parts; Sodium tetraphenylborate, 1.50 parts; Calcium stearate, 1.00 parts.All component mixes and makes the film that thickness is incurable disease 1.3 mils (25-75 micron).After under the 75-105 ℃ of temperature 3 hours, film solidifies fully, has the calcium ion selection function.Then, the film of this prescription and traditional calcium ion selective membrane compare.Obtain this comparative result and discussion hereinafter.
The calcium ion selective film that Comparative Examples 1 is traditional
Formulation solvent base calcium ion selective membrane with traditional compares itself and calcium ion selective membrane of the present invention.This film uses: N, N, N ', N '-Fourth Ring-3-oxygen pentane diamides, 10 milligrams; 2-nitrobenzophenone Octyl Ether, 655 milligrams; Four (4-chlorphenyl) potassium borates, 6 milligrams; HMW PVC, 328 milligrams.All component is dissolved in 8.0 milliliters of (11256 milligrams) oxolanes.Therefore, the gross mass before the solvent evaporation is 12255 milligrams-Yue 8% solid and about 92% solvent.Use traditional method casting film and solidify the film that generates and have the calcium ion selection function.
Utilization can prepare such conventional film greater or less than employed quantity of solvent (in restricted portion) in Comparative Examples.According to the optimised quantity that obtains the institute's solution viscosity that requires use solvent by system film parameter.Can not disperse and be not suitable for settling into evenly flat layer with the solution of very little solvent preparation is general too sticking.The solution that contains excessive solvent is not too sticking, but the evaporation time that will rectificate and longer dispersion and the curing schedule of general also requirement reach specific film thickness.
In this Comparative Examples and the application in other Comparative Examples solutions employed viscosity approximately and in the general manufacture method of these conventional film the viscosity of employed solution identical.Therefore, the measurement of quality or volume loss is the representative of quality or volume loss during traditional solvent basement membrane, ion-selective membrane are made during the solidification process of Comparative Examples film.
Embodiment 2 potassium ion selectives do not have solvent membrane
Potassium ion selective does not have solvent membrane by following formulation: super high molecular weight PVC, 100.00 parts; Dioctyl adipate, 150.00 parts; Valinomycins (potassium ion selective part), 2.85 parts; Sodium tetraphenylborate, 2.00 parts; Stearic acid, 1.00 parts.Make the film of thickness after all component mixes for about 1-3 mil (25-75 micron).At 85-115 ℃ after 6 hours, film solidifies fully, and potassium ion is had selection function.The film of this prescription and traditional potassium ion selective film compare.The result who obtains comparison also discusses hereinafter.
The potassium ion selective film that Comparative Examples 2 is traditional
Utilize traditional formulation potassium ion selective film, itself and potassium ion selective film of the present invention are compared.This film utilizes following formulation: valinomycins, 10 milligrams; Two (1-butyl phenyl) decane-1,10-two basic biglutarates, 650 milligrams; Four (4-chlorphenyl) potassium borates, 5 milligrams; HMW PVC, 330 millis.All component is dissolved in 8.0 milliliters of (11256 milligrams) oxolanes.Therefore, the gross mass of this prescription is 12251 milligrams-Yue 8% solid and about 92% solvent before the solvent evaporation.Utilize traditional technology casting film and curing, the film of preparation has selectivity function to potassium ion.
Embodiment 3 ammonium ion selectivity do not have the film of solvent
The ammonium ion selectivity does not have the film of solvent by following formulation: super high molecular weight PVC, 100.00 parts; Two (ethylhexyl) adipate ester, 250.00 parts; Nonactin (ammonium ion selective ligand), 1.50 parts; The tetraphenyl ammonium borate, 0.36 part; Stearic acid, 1.00 parts.Make the film of thickness after all component mixes for about 1-3 mil (25-75 micron).After 6 hours, film solidifies fully and ammonium ion is had selectivity function 85-105 ℃ of temperature.The film of this prescription and traditional ammonium ion selective film compare.Obtain the result of comparison and discussion hereinafter.
Comparative Examples 3 traditional ammonium ion selective films
Utilize traditional formulation solvent base ammonium ion selective film, compare with ammonium ion selective film of the present invention.The conventional formulation of making this film is: nonactin (ammonium ion selective ligand), 10 milligrams; Two (butyl phenyl) adipate ester, 668 milligrams; HMW PVC, 322 millis.All component is dissolved in 8.0 milliliters of (11256 milligrams) oxolanes.Therefore, the gross mass of this prescription is 12256 milligrams-Yue 8% solid and about 92% solvent before the solvent evaporation.Utilize traditional technology casting film and curing, the film of preparation has selectivity function to potassium ion.
Embodiment 4 solidifies mass loss
In solidification process,, therefore there is not mass loss because film of the present invention does not contain solvent.Otherwise, the prior art ion selective membrane, owing to be to use solvent to make, mass loss is obvious when solvent evaporates.Solidifying mass loss (CML) is a number of expression film quality loss percentage in solidification process, is significant information and measurable difference between film of the present invention and the prior art film therefore.
CML can calculate divided by 100 percentage concentrations that subtract solvent according to the related concentrations in each component of solvent based mixtures.Certainly, this hypothesis solvent is removed fully.Before curing, CML also can determine by the complete cured film of weighing He producing in solidification process afterwards of a certain amount of solvent basement membrane solution with weighing experience.Table 2 provides the film of prior art and the CML calculated value that the present invention does not have solvent membrane.
The CML theoretical value 0% of film of the present invention, the CML measured value is generally less than 10%, preferably less than 1%, is more preferably less than 0.1%.
Table 2 solidifies mass loss
| Film | ????CML(％) |
| There is not solvent calcium ion selective film | ????＜0.1 |
| Traditional calcium ion selective film | -(pact) 92 |
| There is not solvent potassium ion selective film | ????＜0.1 |
| Traditional potassium ion selective film | -(pact) 92 |
| There is not solvent ammonium ion selective film | ????＜0.1 |
| Traditional ammonium ion selective film | -(pact) 92 |
When film solidified, similar to mass loss was the volume loss of film.The volume loss of film of the present invention is very little, and if any, volume changes after curing.Otherwise it is 91.6% (potassium ion selective film) and 89.3% (ammonium ion selective film) that the film of Comparative Examples demonstrates the volume loss.Volume loss to traditional calcium ion selective film is not measured.
Embodiment 5 water absorption indexs
There are marked difference in film of the present invention and prior art organic ion optionally film, and this is because they have reduced the trend that absorbs water widely.The functional importance of this difference has been discussed above.The useful measurement of this difference is water absorption index (WAI).WAI measured by at room temperature the membrane sample of known quality being inserted in the distilled water in 24 hours.After 24 hours, this sample is weighed again, and if any, quality comes the percentage of quality to represent with pleurodiaphragmatic in terspace again.Then, according to separately WAI can comparative film difference.
Though being the water uptake, measures WAI with choosing at random,, it is the simple and general test of the water affinity difference of different films that is directly proportional with the water affinity of different films and shows.According to the special ion selective membrane that plan to use, similar to WAI other test as above also can be used.
For example, under body temperature, during a week in, utilize blood plasma absorption index to fail to show resemble the aqueous solution, during one week of implantable bioartificial sensor electrode, the deformation extent of different formulations film.Use contains the purpose ion solution also can carry out the test of purpose ion selective membrane, in many cases, except that containing the purpose ion, also can contain other additive, as chelating agent, pH buffer and/or the antiseptic solution of not wishing ion.Though WAI provides a kind of simple and general comparison basis,, to the film studied more specifically other solution can be used for relatively quickening the test that water absorbs, the difference between can rapider detection film.Referring to embodiment 7.
Film of the present invention absorbs the ion selective membrane much less of water than prior art, and is therefore more stable when contacting with the aqueous solution, shown as following table 3.Usually, the WAI of film of the present invention is less than 0.5%, preferably less than 0.1%, is more preferably less than 0.05%.
Table 3 water absorption index (WAI)
| Film | ????WAI(％) |
| There is not solvent calcium ion selective film | ????＜0.1 |
| Traditional calcium ion selective film | ????0.69 |
| There is not solvent potassium ion selective film | ????＜0.2 |
| Traditional potassium ion selective film | ????0.95 |
| There is not solvent ammonium ion selective film | ????＜0.1 |
| Traditional ammonium ion selective film | ????0.72 |
The result who lists for instruction card 3 clearly, if 1000 milligrams of dry films are as raw material, after 24 hours, the weight of film of the present invention is between 1000 milligrams and 1002 milligrams in water, and traditional potassium ion selective film weight after 24 hours in water is 1009.5 milligrams.
The loss of embodiment 6 water quality
Another advantage of film of the present invention is that because they do not absorb water and reach suitable degree, the loss of membrane component does not take place to cause because of the leaching that absorbs the generation of water and/or permeability equally for they.Otherwise in fact traditional solvent base ion selective membrane has mass loss, the reason that the chances are runs off owing to membrane component inner in contact 24 hours process with water.
As the step after embodiment 5, in water, after 24 hours the film dry tack free of immersion, removed residual moisture in 24 hours in air drying.Gan Zao film is weighed again then, each soak and the quality of desciccator diaphragm its original quality compares with being immersed in the water before.As shown in table 4, traditional film has mass loss, and film of the present invention does not demonstrate tangible mass change.
Table 4 water quality loss (WML)
| Film | ????WML(％) |
| There is not solvent calcium ion selective film | ????＜0.1 |
| Traditional calcium ion selective film | ????0.45 |
| There is not solvent potassium ion selective film | ????＜0.2 |
| Traditional potassium ion selective film | ????0.61 |
| There is not solvent ammonium ion selective film | ????＜0.1 |
| Traditional ammonium ion selective film | ????0.54 |
Be the result of instruction card 4 clearly, if 1000 milligrams of dry films are as raw material, film of the present invention is in water after 24 hours, subsequently in the weight of air after dry 24 hours between 1000 milligrams and 998 milligrams, and traditional potassium ion selective film is in water after 24 hours, and then the weight behind air drying 24 is 993.9 milligrams.
Embodiment 7 solions absorb
When measuring solution by their and measure the distortion of prior art film, the solution of film that perhaps more meaningfully contains these films of object ion than WAI absorbs.That is to say, increase more quality when contacting when traditional calcium ion selective film contacts with calcium solution than with deionized water.
This is that hypothesis is because the cause of the affinity of selectivity agent of film intermediate ion and effects of ion.When film absorbs water, it is believed that ion also enters the active ingredient interaction of film and film.Then, Nei Bu ion accumulation also can cause the accumulation of more water.Consequently film absorbent solution incurs loss malformation and function.Otherwise film of the present invention does not demonstrate tangible solion and absorbs.In fact, of the present invention do not have no matter the film of solvent is to contact with solion or with deionized water, all do not demonstrate measurable difference.
Is to have optionally to measure the solion absorption in the ion solution by membrane sample being inserted the film that contains 4 milligrams of milliequivalents (m eq) to this ion.Film at room temperature stopped in this solion 24 hours, blotted then and weighed.The film of prior art demonstrates the obvious quality that increased, and in film of the present invention near being increased in detectability or the detectability of quality.
Table 5 solion absorbs (ISA)
| Film | ??ISA(％) |
| There is not solvent calcium ion selective film | ????＜0.1 |
| Traditional calcium ion selective film | ????2.37 |
| There is not solvent potassium ion selective film | ????＜0.2 |
| Traditional potassium ion selective film | ????1.83 |
| There is not solvent ammonium ion selective film | ????＜0.1 |
| Traditional ammonium ion selective film | ????1.16 |
Embodiment 8 solions stop
In the ion absorption experiment of embodiment 7, film is to weigh after dry 24 hours with air again.After dry 24 hours, conventional film keeps quality from solion, and film of the present invention does not demonstrate tangible mass change.
Table 6 solion keeps (ISR)
| Film | ??ISR(％) |
| There is not solvent calcium ion selective film | ????＜0.1 |
| Traditional calcium ion selective film | ????0.39 |
| There is not solvent potassium ion selective film | ????＜0.2 |
| Traditional potassium ion selective film | ????0.47 |
| There is not solvent ammonium ion selective film | ????＜0.1 |
| Traditional ammonium ion selective film | ????0.47 |
The foregoing description proves that ion selective membrane of the present invention makes remarkable progress, and these embodiment only are the more representational schemes of the present invention.The present invention's scope is accurately only defined by following claim.
Claims (41)
1. method for preparing ion selective membrane, the method comprising the steps of:
Provide and comprise polymer and at least a membrane component that the additive of ion selectivity is provided;
Above-mentioned component is mixed, generate the mixture that does not add solvent; With
Generate ion selective membrane from said mixture.
2. by the process of claim 1 wherein that polymer contains vinyl chloride.
3. by the method for claim 2, wherein polymer is a polyvinyl chloride.
4. by the method for claim 2, wherein polymer is the copolymer of vinyl chloride.
5. by the method for claim 4, wherein said copolymer contains vinyl acetate.
6. by the method for claim 4, wherein said copolymer contains vinyl alcohol.
7. by the process of claim 1 wherein that described additive is a kind of plasticizer.
8. by the method for claim 7, wherein said plasticizer is selected from the group of being made up of aromatic ether, aliphatic-aromatic ether, adipate ester, sebacate, phthalic acid ester, laurate, glutarate and phosphate.
9. by the process of claim 1 wherein that described additive is a kind of ion selectivity agent.
10. by the process of claim 1 wherein that described membrane component comprises that more than one state additive.
11. by the method for claim 10, wherein said membrane component comprises a kind of plasticizer and a kind of ion selectivity agent.
12. by the method for claim 11, wherein said membrane component further comprises and is selected from a kind of additive of being made of group plasticizer modifier, active ingredient, ionic mobility reinforcing agent, heat stabilizer, light stabilizer, surface-active modifier, lipophilic agent and center fixed agent.
13. by the process of claim 1 wherein that above-mentioned blend step is included in mixing said ingredients in the homogenizer.
14. by the process of claim 1 wherein that above-mentioned blend step comprises the heating said components.
15. said mixture is squeezed on the device of the described film of suitable use by the process of claim 1 wherein that above-mentioned forming step comprises.
16. by the process of claim 1 wherein that described forming step comprises that the described mixture of injection moulding generates described film.
17. the method by claim 1 also comprises:
Biomolecule and described component reaction generate a described biomolecule and a key between the described film of described film surface.
18. by the method for claim 17, wherein above-mentioned biomolecule is selected from the group of being made up of enzyme, acceptor class, steroids, nucleic acid and antibody.
19. by the method for claim 1, further comprise: the surface of described film contacts with the water-containing materials that comprises biomolecule, generates to comprise the two-layer ion selective membrane that does not have solvent layer and water-bearing layer.
20. by the method for claim 19, wherein said biomolecule is selected from the group of being made up of enzyme, acceptor class, steroids, nucleic acid and antibody.
21. do not have the ion selective membrane of solvent, described film comprises membrane component, described membrane component comprises a kind of polymer and at least a additive that ion selectivity character is provided, and described film is not have solvent to make.
22. by the film of claim 21, wherein said polymer contains vinyl chloride.
23. by the film of claim 22, wherein said polymer is a polyvinyl chloride.
24. by the film of claim 22, wherein said polymer is the copolymer of vinyl chloride.
25. by the film of claim 24, wherein said copolymer comprises vinyl acetate.
26. by the film of claim 24, wherein said copolymer comprises vinyl alcohol.
27. by the film of claim 25, wherein said additive is a kind of plasticizer.
28. by the film of claim 27, wherein said plasticizer is selected from by aromatic ether, aliphatic-aromatic ether, adipate ester, sebacate, phthalic acid ester, laurate, glutarate and phosphate forms group.
29. by the film of claim 21, wherein said additive is a kind of ion selectivity agent.
30. by the film of claim 21, wherein said membrane component comprises more than one additive.
31. by the film of claim 30, wherein said membrane component comprises a kind of plasticizer and a kind of ion selectivity agent.
32. by the film of claim 31, wherein said membrane component further comprises and is selected from a kind of additive of being made of group plasticizer modifier, active ingredient, ionic mobility reinforcing agent, heat stabilizer, light stabilizer, surface-active modifier, lipophilic agent and center fixed agent.
33. the film by claim 21 wherein solidifies mass loss less than 10%.
34. the film by claim 33 wherein solidifies mass loss less than 1%.
35. by the film of claim 21, the water absorption index is less than 0.5%.
36. by the film of claim 35, the water absorption index is less than 0.1%.
37. the film by claim 21 further comprises being keyed to the lip-deep biomolecule of above-mentioned film.
38. by the film of claim 37, wherein said biomolecule is selected from the group of being made up of enzyme, acceptor class, steroids, nucleic acid and antibody.
39., comprise that further the one deck that contacts with described film surface comprises the water-containing materials of biomolecule by the film of claim 21.
40. by the film of claim 39, wherein said biomolecule is selected from the group of being made up of enzyme, acceptor class, steroids, nucleic acid and antibody.
41. in a kind of improved biosensor arrangement, this biosensor arrangement comprises that an electrode, described electrode comprise an ion selective membrane, is characterized in that:
The ion selective membrane that does not have solvent, described film comprises membrane component, and described component comprises a kind of polymer and at least a additive that ion selectivity character is provided, and described film is not have solvent to make.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5589598A | 1998-04-06 | 1998-04-06 | |
| US09/055,895 | 1998-04-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1302223A true CN1302223A (en) | 2001-07-04 |
Family
ID=22000867
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 99806501 Pending CN1302223A (en) | 1998-04-06 | 1999-03-29 | Organic ion-selective membranes |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1069938A1 (en) |
| JP (1) | JP2002510540A (en) |
| CN (1) | CN1302223A (en) |
| AU (1) | AU3214199A (en) |
| CA (1) | CA2330463A1 (en) |
| WO (1) | WO1999051330A1 (en) |
| ZA (1) | ZA200006298B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103336044A (en) * | 2013-06-18 | 2013-10-02 | 南京普朗医疗设备有限公司 | All solid-state ion selective electrode and preparation method and application thereof |
| CN112384792A (en) * | 2018-07-04 | 2021-02-19 | 雷迪奥米特医学公司 | Magnesium ion selective PVC membrane |
| CN114778646A (en) * | 2022-03-24 | 2022-07-22 | 南京工业大学 | Ammonium ion selective electrode sensitive membrane and preparation method and application thereof |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102004044299A1 (en) * | 2004-09-10 | 2006-03-30 | Forschungszentrum Jülich GmbH | Apparatus and method for detecting charged macromolecules |
| WO2016156941A1 (en) * | 2015-04-03 | 2016-10-06 | Diasys Diagnostics India Private Limited | Solid state electrolyte biosensor |
| EP3818364A1 (en) * | 2018-07-04 | 2021-05-12 | Radiometer Medical ApS | Ion selective membranes and the preparation thereof |
| CN112384793B (en) * | 2018-07-04 | 2023-05-30 | 雷迪奥米特医学公司 | Magnesium ion selective membrane |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB743926A (en) * | 1953-05-18 | 1956-01-25 | Pritchett & Gold & E P S Co Ltd | Improvements relating to diaphragms for use in ion exchange processes |
| GB810391A (en) * | 1956-06-07 | 1959-03-18 | Permutit Co Ltd | Improvements in and relating to ion-exchange membranes |
| GB950725A (en) * | 1959-06-30 | 1964-02-26 | Permutit Co Ltd | Improvements relating to ion-selective membranes |
| AT268204B (en) * | 1963-07-22 | 1969-02-10 | Metrimpex Magyar Mueszeripari | Ion-selective membranes and processes for their manufacture |
| US4931172A (en) * | 1988-06-02 | 1990-06-05 | E. I. Du Pont De Nemours And Company | Fluoride ion-selective electrodes based upon superionic conducting ternary compounds and methods of making |
| CA1316572C (en) * | 1988-07-18 | 1993-04-20 | Martin J. Patko | Precalibrated, disposable, electrochemical sensors |
| US5453171A (en) * | 1992-03-10 | 1995-09-26 | The Board Of Regents Of The University Of Michigan | Heparin-selective polymeric membrane electrode |
| US5346924B1 (en) * | 1992-09-23 | 2000-04-25 | Ionpure Techn Corp | Heterogenous ion exchange materials comprising polyethylene of linear low density or high density high molecular weight |
| EP0792454B1 (en) * | 1994-11-14 | 2002-04-10 | Bayer Corporation | RANDOMLY SEGMENTED THERMOPLASTIC POLYURETHANES AS MATRIX FOR ELECTROCHEMICAL ANALYSIS OF Ca++ IONS |
| US5738774A (en) * | 1995-07-28 | 1998-04-14 | The Governors Of The University Of Alberta | Eva containing ion selective membranes and methods of making same |
-
1999
- 1999-03-29 JP JP2000542092A patent/JP2002510540A/en active Pending
- 1999-03-29 AU AU32141/99A patent/AU3214199A/en not_active Abandoned
- 1999-03-29 WO PCT/US1999/006832 patent/WO1999051330A1/en not_active Application Discontinuation
- 1999-03-29 CA CA002330463A patent/CA2330463A1/en not_active Abandoned
- 1999-03-29 EP EP99914252A patent/EP1069938A1/en not_active Withdrawn
- 1999-03-29 CN CN 99806501 patent/CN1302223A/en active Pending
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2000
- 2000-11-03 ZA ZA200006298A patent/ZA200006298B/en unknown
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103336044A (en) * | 2013-06-18 | 2013-10-02 | 南京普朗医疗设备有限公司 | All solid-state ion selective electrode and preparation method and application thereof |
| CN103336044B (en) * | 2013-06-18 | 2015-03-11 | 南京普朗医疗设备有限公司 | All solid-state ion selective electrode and preparation method and application thereof |
| CN112384792A (en) * | 2018-07-04 | 2021-02-19 | 雷迪奥米特医学公司 | Magnesium ion selective PVC membrane |
| CN112384792B (en) * | 2018-07-04 | 2023-05-30 | 雷迪奥米特医学公司 | Magnesium ion selective PVC film |
| CN114778646A (en) * | 2022-03-24 | 2022-07-22 | 南京工业大学 | Ammonium ion selective electrode sensitive membrane and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1069938A1 (en) | 2001-01-24 |
| CA2330463A1 (en) | 1999-10-14 |
| WO1999051330A1 (en) | 1999-10-14 |
| AU3214199A (en) | 1999-10-25 |
| ZA200006298B (en) | 2001-11-07 |
| JP2002510540A (en) | 2002-04-09 |
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