CN105203605A - Calcium ion biochemical analysis dry slice and preparation method thereof - Google Patents
Calcium ion biochemical analysis dry slice and preparation method thereof Download PDFInfo
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- CN105203605A CN105203605A CN201510695386.7A CN201510695386A CN105203605A CN 105203605 A CN105203605 A CN 105203605A CN 201510695386 A CN201510695386 A CN 201510695386A CN 105203605 A CN105203605 A CN 105203605A
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Abstract
The invention relates to a calcium ion biochemical analysis dry slice and a preparation method thereof, relates to the technical field of blood gas biochemical transducers. The calcium ion biochemical analysis dry slice is used for detecting the concentration of calcium ions in body fluid. The dry slice comprises a support layer, an insulation layer, a salt bridge, an electrode, a reference layer and a calcium ion selective membrane. The preparation method comprises the steps that a metal/metal salt thin slice electrode is prepared; the reference layer is attached onto the electrode; the ratio of sodium chloride and calcium chloride and the water content in the reference layer are constant; the calcium ion selective membrane is attached onto the reference layer to prepare calcium ion selective electrodes; the calcium ion selective membrane uses acrylate as bonding agent; the salt bridge is sealed in the insulation layer; two calcium ion selective electrodes are adhered to the support layer and the insulation layer to assemble the dry slice; the liquid to be tested is conducted with the reference liquid through the salt bridge during testing. According to the prepared dry slice, the defects of operation complexity, high use and maintenance cost, slow response and difficulty in carrying of the conventional ion selective electrodes can be overcome; the dry slice is simple to operate, high in response speed, small in size, simple in preparation process and low in production cost; the dry slice is suitable for industrial production.
Description
Technical field
The present invention relates to vim and vigour biochemical sensor technologies field, particularly relate to a kind of calcium ion biochemical analysis dry plate and preparation method thereof.
Background technology
Calcium is one of indispensable element of body vital movement, about containing 1kg in adult body.Calcium ion is the kation that in blood, content is maximum, belongs to physiological activator, in the research and some medical diagnosis on disease relevant with calcium metabolism clinical thereof of physiological function, measures calcium ion concentration significant.
Calcium ion-selective electrode method can directly measure calcium ion concentration in blood.Traditional wet type biochemical analysis detect have that complicated operation, operation and maintenance cost are high, low-response, the shortcoming such as not portable.Novel electrolyte detection method---dry type detects, and has and measures the features such as accurate, with low cost, simple to operate, can be widely used in multiple environment for use.
Chinese patent CN104849335A discloses a kind of method detecting blood sample calcium ion content, and it adopts wet type biochemical analysis detection method, and complicated operation, response speed are slow, and not portable.Existing patent adopts screen printing technique to prepare electrode substantially, but the metal level purity that serigraphy obtains is inadequate, and surface is uneven, can affect stability and the response time of electromotive force.And in existing solid ionic choice electrode, all select Polyvinylchloride as the high polymer binder (patent CN101852761A, CN104330449A, CN102636532A, CN101871912A, CN102558724A etc.) of ion-selective membrane.Polyvinylchloride has higher intensity and chemical stability, and low price, but it must add plastifier just can guarantee that ion-selective membrane responds, As time goes on, plastifier be dissolved in carrier wherein can together with leak out from ion-selective membrane, cause ion-selective membrane to respond lower limit to be deteriorated, lifetime.
Summary of the invention
For existing calcium ion-selective electrode Problems existing, the invention provides a kind of calcium ion biochemical analysis dry plate and preparation method thereof, prepared dry plate measuring accuracy is high, long-time stability are good, response time is short, and structure is simple, volume is little, and preparation technology is simple, production cost is low, is applicable to producing in enormous quantities.
Calcium ion biochemical analysis dry plate of the present invention comprises supporting layer, insulation course, salt bridge, electrode, reference layer and calcium ion selective membrane.Preparation technology is as follows: (1) prepares metal/metal salt thin electrode; (2) on electrode, the reference layer solution prepared and calcium ion selective membrane solution is coated with and calcium ion-selective electrode is prepared in drying; (3) convince pore by patient analysis on the insulating layer, salt bridge is sealed in insulation course; (4) by two panels calcium ion-selective electrode and supporting layer, the bonding assembling dry plate of insulation course.
In the present invention, supporting layer plays protection, supports calcium ion-selective electrode effect, and insulation course plays bonding electrode, the effect of sealing salt bridge, and salt bridge plays the effect of connection electrode; Insulation course has gas port, the flow rate of reference liquid and test fluid during test, can be improved, shorten the test duration; Supporting layer, insulation course are selected from polypropylene, Polyvinylchloride, tygon, polyester non-conductive polymer material, and salt bridge is filter paper material.
Electrode.Electrode of the present invention comprises metal level and metal salt.Metal salt and metal level form phase boundary potential, have stable electromotive force response.Metal is selected from gold, silver, copper, mercury, platinum, nickel.Slaine is selected from the insoluble metallic salt of metal level metal.Metal salt can use the oxide of metal level metal, such as metal halide.Preferred electrode silver/silver chloride electrode.
Electrode metal layer is attached to non-conductive polymer surface, be improve electrode stability, shorten the response time, the present invention can adopt vacuum coating, the mode of electroless plating or plating prepares metal level, preferred electroless plating method.Use electroless plating method, layer on surface of metal is even, can set up the balance between phase boundary instantaneously, form stable response electromotive force, shortens the response time.Metal salt can adopt the method for chemical oxidation to obtain, and uses iron chloride or liquor potassic permanganate to be oxidized metal level.
Reference layer.Reference composition of layer comprises: cementing agent, slaine, surfactant.Reference layer is directly attached on electrode metal salt deposit by the mode of lamination or coating.
Need in reference layer used herein containing the identical negative ion of electrode metal salt deposit and kation calcium ion to be measured.As requested, in reference layer, slaine lime chloride can be selected, but lime chloride solubleness temperature influence is comparatively large, preferable alloy salt sodium chloride and lime chloride composite.The proportioning of sodium chloride and lime chloride directly can affect and respond potential stability, and the bonding strength of reference layer and ion-selective membrane can be affected, the stability of response can be improved by the proportioning changing sodium chloride and lime chloride, the proportioning of preferred sodium chloride and lime chloride is 1:1, accounts for 20% ~ 50% of reference layer gross mass.
Reference layer binder is selected from one or more in gelatin, agar, polyacrylamide, polyvinyl alcohol (PVA) or other polyvinyl, accounts for 30% ~ 80% of reference layer gross mass.
For ensureing the bond strength of reference layer and calcium ion selective membrane, prevent calcium ion biochemical analysis dry plate response signal accuracy and long-time stability from reducing, reference layer water cut can not be too high or too low, and reference layer optimum moisture content is 30% ~ 40%.
The present invention by controlling drying time of reference layer, temperature, humidity fixes sodium chloride and lime chloride proportioning and water cut in reference layer, preferred drying condition: 25 DEG C, relative humidity 50%, dry 40min.
Calcium ion selective membrane.Calcium ion selective membrane composition comprises: high polymer binder, ionophore, carrier solvent, negative ion agent interfering, surfactant.
For reducing the consumption of plastifier, reduce carrier and run off, promote the long-time stability of calcium ion selective membrane, the high polymer binder that the present invention uses is acrylate materials.Its physical and mechanical property is controlled, can reduce the use of plastifier, and the physical property of its excellence can promote the adhesion property of ion-selective membrane and solid electrolyte reference layer simultaneously, improves the stability of the response signal of ion-selective electrode.Acrylate has lower coefficient of diffusion, is conducive to obtaining wider sensing range, and less coefficient of diffusion be conducive to carrier dispersed and suppress carrier run off, eliminate carrier run off on response electromotive force impact, improve the accuracy of test.Esters of acrylic acid cementing agent is selected from one or more in ethyl acrylate, methyl acrylate, methyl methacrylate, β-dimethyl-aminoethylmethacrylate, glycidyl methacrylate, methacrylic acid ester in the positive last of the ten Heavenly stems, preferable methyl methyl acrylate, accounts for 10% ~ 50% of calcium ion selective membrane gross mass.
Ionophore selects compound calcium ion to selective response, and carrier is selected from (-)-(R, R)-N, N-bis--[11-(carbethoxyl group) undecyl]-N, N ', 4, 5-tetramethyl-3,6-dioxaoctane-diamides, diethyl N, N '-[(4R, 5R)-4, 5-dimethyl-1, 8-dioxo-3, 6-dioxa Ya Xinji] two (12-methylamino lauric acid (ETH1001), N, N, N ', N '-four [cyclohexyl] diglycolic acid diamides N, N, N ', N '-four cyclohexyl-3-oxa-glutaryl (ETH129), Calcimycin (A23187), the tert-butyl group-cup [4] aromatic hydrocarbons four [2-(diphenylphosphoryl) ether], 10, two [(octadecylamino formoxyl) Methoxyacetyl]-1 of 19-, 4, 7, 13, 16-five oxa--10, one in 19-diazacyclo heneicosane (K23E1), account for 0.1% ~ 10% of calcium ion selective membrane gross mass.
Carrier solvent requires energy dissolved ions carrier, and has good compatibility with high polymer binder, guarantees that carrier moves in high polymer binder.Usual carrier solvent can be used as macromolecular material plastifier and uses, and is selected from one or more in phthalic ester, sebacate, ortho-nitrophenyl octyl ether, adipate mixing aromatic aliphatic phosphate, accounts for 20% ~ 80% of calcium ion selective membrane gross mass.
Negative ion agent interfering requires to dissolve in carrier solvent, anions (as long-chain fatty acid, long chain alkyl sulphonates or long-chain Acidic phosphates salt) can be got rid of near ion-selective membrane, reduce and ionophore is optionally disturbed, improve the sensitivity of electrode pair cation selective, expand the linear response range of ion-selective electrode.Be selected from one or more in tetraphenylboron sodium, tetraphenylboron calcium, four (4-chlorphenyl) line borate, four [two (trifluoromethyl) phenyl of 3,5-] sodium borate, usually account for 0.1% ~ 5% of calcium ion selective membrane gross mass.
Surfactant is selected from one or more in organosilicon or siloxane type surfactants, accounts for 0.1% ~ 5% of calcium ion selective membrane gross mass.
Be different from calcium ion-selective electrode in existing patent, major advantage of the present invention has: (1) eliminates liquid electrolyte layer, adopts structure of whole solid state, convenient and swift, does not need long-time activation during use; (2) by sodium chloride in adjustment reference layer and lime chloride proportioning, fixing reference layer water cut, and use the high polymer binder that acrylate is calcium ion selective membrane, promote measuring accuracy and the long-time stability of calcium ion biochemical analysis dry plate; (3) the metal/metal salt thin electrode surface uniform prepared, shortens the calcium ion biochemical analysis dry plate response time greatly, can equilibrium establishment within 7s, forms stable response electromotive force; (4) structure is simple, volume is little, and size is 10mm × 10mm, is easy to integrated, can be developed into superminiature biochemical analysis dry plate, and preparation technology is simple, with low cost, is suitable for large-scale industrial production.
Accompanying drawing explanation
Fig. 1 is calcium ion biochemical analysis dry plate schematic diagram.
Fig. 2 is calcium ion-selective electrode (electrode, reference layer, ion-selective membrane) schematic diagram.
Fig. 3 is calcium ion biochemical analysis dry plate testing standard liquid response potential curve.
Fig. 4 is calcium ion selective membrane test variable concentrations CaCl
2solution response electromotive force.
Fig. 5 is calcium ion biochemical analysis dry plate family curve.
Fig. 6 is calcium ion biochemical analysis dry plate long term stability tests result.
Embodiment
The present invention is described in detail with embodiment by reference to the accompanying drawings.
As shown in Figure 1, calcium ion biochemical analysis dry plate comprises: supporting layer 1, calcium ion-selective electrode 2, insulation course 3, salt bridge 4.
As shown in Figure 2, calcium ion-selective electrode comprises: silver layer 21, silver chloride layer 22, reference layer 23, calcium ion selective membrane 24.
Concrete implementation step is as follows.
By the method for electroless plating at polyethylene terephthalate plated surface silver layer, prepare silver layer 21.
Chemical method is adopted to be oxidized by front for silver layer 21 2/3 section.The contact electrode being oxidized position will be needed to be immersed in 0.1mol/L ferric chloride solution after 60s, and taking-up pure water cleans up and drying, obtains silver chloride layer 22.
Reference layer is coated with.By 6g polyvinyl alcohol (PVA), 1g glycerine, 1g sodium chloride, 1g lime chloride, 0.02g germifuge, 0.004g surfactant H212 is dissolved in 100g water, is coated on silver chloride layer 22, drying condition: 25 DEG C, relative humidity 50%, 60min.
Calcium ion selective membrane is coated with.By 0.1g methyl methacrylate, 0.1g ortho-nitrophenyl octyl ether, 0.005g Calcimycin, 0.002g tetraphenylboron sodium, 0.005g surfactant H212 is dissolved in ethyl acetate, and coats on reference layer 23, and drying at room temperature.
After calcium ion selective membrane 24 drying is complete, get two panels calcium ion-selective electrode 2 bonding with insulation course 3, by bonding with supporting layer 1 for insulation course 3 assembling dry plate after solidification.
Calcium ion biochemical analysis dry plate long-term storage conditions is :-18 ~-10 DEG C.
Calcium ion biochemical analysis dry plate using method, uses after needing to place 1h at normal temperatures when taking out from low temperature environment, keeps probe temperature 37 ± 0.1 DEG C during test.During test, dry plate is inserted in test trough, two lateral opening dropping reference liquid and test fluid respectively, required sample 5 ~ 10 μ L.
In order to advantage of the present invention is better described, the invention provides 4 groups of experimental datas, specific as follows.
Experiment 1, the response electromotive force of calcium ion biochemical analysis dry plate testing standard liquid, response electromotive force and the curve of test duration are as shown in Figure 3.
Experiment 2, prepares calcium ion selective membrane test variable concentrations CaCl
2solution (0.25mmol/L, 2.5mmol/L, 25mmol/L) responds electromotive force, and test result as shown in Figure 4.
Experiment 3, calibrates calcium ion biochemical analysis dry plate.By known calcium ion concentration titer (calcium ion concentration 0.49mmol/L and 3.57mmol/L), test calcium ion biochemical analysis dry plate response electromotive force, obtains electromotive force response corrections curve.Correction equation is: Y=31.1X+6.34, and wherein Y represents response electromotive force, and X represents logC, and C is calcium ion concentration in solution.Family curve as shown in Figure 5.
Experiment 4, calcium ion biochemical analysis dry plate long term stability tests, with the response electromotive force of measurement standard liquid (calcium ion concentration 0.49mmol/L) respectively in the calcium ion biochemical analysis dry plate 90 days of a collection of preparation, test result as shown in Figure 6.
The above its object is to person skilled in the art can be understood content of the present invention and implement according to this only for technical conceive of the present invention and feature are described, can not limit the scope of the invention with this.All modifications done according to the Spirit Essence of main technical schemes of the present invention, all should be encompassed within protection scope of the present invention.
Claims (9)
1. calcium ion biochemical analysis dry plate and preparation method thereof, is characterized in that: described calcium ion biochemical analysis dry plate comprises supporting layer, insulation course, salt bridge, electrode, reference layer and calcium ion selective membrane; The main preparation process of described calcium ion biochemical analysis dry plate comprises, and (1) prepares metal/metal salt thin electrode; (2) on electrode, the reference layer solution prepared and calcium ion selective membrane solution is coated with and calcium ion-selective electrode is prepared in drying; (3) convince pore by patient analysis on the insulating layer, salt bridge is sealed in insulation course; (4) by two panels calcium ion-selective electrode and supporting layer, the bonding assembling dry plate of insulation course.
2. salt bridge, supporting layer, insulation course according to claim 1, it is characterized in that: described salt bridge is filter paper material, described supporting layer and insulation course are selected from polypropylene, Polyvinylchloride, tygon and polyester non-conductive polymer material.
3. supporting layer, insulation course according to claim 1, is characterized in that: described supporting layer and insulation course are schistose texture, thickness 0.5 ~ 2mm.
4. electrode according to claim 1, is characterized in that: described electrode is metal/metal salt thin electrode, and electrode comprises metal level and metal salt; Metal level metal is selected from gold, silver, copper, mercury, platinum, nickel; Slaine is selected from the insoluble metallic salt of metal level metal.
5. electrode according to claim 1, is characterized in that: described electrode adopts electroless plating, the mode of Vacuum Deposition or plating is attached on substrate, metal level and metal salt thickness 0.1 ~ 10 μm on substrate.
6. reference layer according to claim 1, is characterized in that: described reference layer comprises bonding agent, slaine, surfactant; Slaine is that sodium chloride and lime chloride are composite, and proportioning is 1:1 ~ 8:1, accounts for 20% ~ 80% of reference layer gross mass.
7. reference layer according to claim 1, is characterized in that: described reference layer is attached on electrode, baking temperature 20 ~ 50 DEG C, dry environment relative humidity 25% ~ 50%, drying time 30 ~ 90min, reference layer water cut 20% ~ 50%.
8. calcium ion selective membrane according to claim 1, is characterized in that: described calcium ion selective membrane comprises polymeric adhesive, ionophore, carrier solvent, negative ion agent interfering, surfactant; Polymeric adhesive is selected from one or more in ethyl acrylate, methyl acrylate, methyl methacrylate, β-dimethyl-aminoethylmethacrylate, glycidyl methacrylate, methacrylic acid ester in the positive last of the ten Heavenly stems, accounts for 10% ~ 50% of calcium ion selective membrane gross mass.
9. calcium ion selective membrane according to claim 1, is characterized in that: described calcium ion selective membrane be attached to dry after on reference layer.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113702467A (en) * | 2020-05-20 | 2021-11-26 | 无锡锦帛诚医疗器械科技有限公司 | Calcium ion quantitative detection dry tablet and preparation method thereof |
| CN115753930A (en) * | 2022-12-06 | 2023-03-07 | 北京乐普诊断科技股份有限公司 | All-solid-state ion selective electrode and preparation method thereof |
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| CN101871912A (en) * | 2010-06-07 | 2010-10-27 | 浙江大学 | A kind of all-solid-state potassium ion sensor and preparation method thereof |
| CN102636532A (en) * | 2012-04-24 | 2012-08-15 | 南京工业大学 | Medical all-solid-state potassium ion selective sensor and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113702467A (en) * | 2020-05-20 | 2021-11-26 | 无锡锦帛诚医疗器械科技有限公司 | Calcium ion quantitative detection dry tablet and preparation method thereof |
| CN115753930A (en) * | 2022-12-06 | 2023-03-07 | 北京乐普诊断科技股份有限公司 | All-solid-state ion selective electrode and preparation method thereof |
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