CN1250968C - Reagent layer ultrasonic direct fixture and method for preparing stirpping test-piece - Google Patents
Reagent layer ultrasonic direct fixture and method for preparing stirpping test-piece Download PDFInfo
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- CN1250968C CN1250968C CN 02156182 CN02156182A CN1250968C CN 1250968 C CN1250968 C CN 1250968C CN 02156182 CN02156182 CN 02156182 CN 02156182 A CN02156182 A CN 02156182A CN 1250968 C CN1250968 C CN 1250968C
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Abstract
The present invention relates to a method for directly fixing a reagent layer on a substrate plate in the process of preparing a dry analytical reagent kit for measuring the content of a specific component in a liquid sample. At least one layer of a reagent layer and a substrate plate is made of thermoplastic resin. The method comprises the steps: the reagent layer is in contact with the substrate plate, and the ultrasonic vibration and the pressure are applied to the two layers from the outer part so as to produce friction heat which is used for melting the surface of the thermoplastic resin; the molten surface of the thermoplastic resin is bounded on a non-thermoplastic material by applying the pressure, or the surface of a thermoplastic layer is combined with the substrate plate; the ultrasonic vibration and the pressure are cancelled.
Description
Technical field
The present invention relates to a kind of method that in the preparation of the dry analysis kit that is used for measuring the fluid sample special component, a reagent layer is fixed on the substrate.This kit is generally used for such as in these clinical examination fields of urinalysis, serum analysis, whole blood and immunoassays.
The invention still further relates to a kind of method for preparing exfoliated test specimen, this test specimen is a kind of dry analysis kit that is used for measuring the whole blood special component, is generally used in the whole blood in clinical examination field.
Background technology
In the clinical examination field, the analysis of various compositions helps to diagnose numerous disease or curative effect is carried out objective judgement in the body fluid (for example blood, urine, saliva, celiolymph etc.).
The conventional method of these analyses is a kind of methods that are called wet-chemical, in this method, at first body fluid (sample) and test solution are put into a cell and stirring, under 37 ℃, cell is incubated one given period then, at last with the material that reaction generated of mensuration such as absorption spectrophotometry, fluorophotometer, nephelometer by the special component of sample.
On the other hand, work out a kind of analytical approach that is called dry chemical.The advantage of this method is that reagent provides with the dry state form, and the preparation of reagent is not fully essential in analysis, need not to stir, and no waste liquid occurs, and very small amount of sample is just enough analyzed numerous items.Utilize dry chemical in the nurses' office of the first-aid room of hospital, night hospital or doctor's office, to carry out real-time test.
Used dry analysis kit generally includes a reagent layer and a underboarding in the dry chemical.Can be prepared as follows reagent layer, soon the reagent that can react with certain composition in the sample infiltrates in a kind of porous matrix (for example paper, cloth, nonwoven fabrics, screen cloth, film filter paper, sinter and pottery), dry then, perhaps the potpourri with the polymer adhesive of reagent and a kind of solvent bonding is applied on the thin resin film, and is dry then.When the reagent layer that utilization like this is cut into inch strips, when promptly utilizing such as enzyme, substrate or these expensive reagent of color product, it is uneconomic using the big strip of useful area, can cause cost to rise significantly.
Therefore, consider the accuracy of beam diameter used in the size that can carry out visual colorimetry, the reflection photometry, measured value and easy operating in preparation or in using, reagent layer is cut into 4 to 10mm square or rectangular.Reagent layer after for example double-faced adhesive tape, paste adhesive or instantaneous adhesive or thermoplastic resin will cut with bonding agent is fixed in the substrate as bottom or handle.
And the so-called exfoliated test specimen of the dry analysis kit that is used for dry chemical of Li Yonging comprises that one has a reagent layer and the substrate with taken off thin layer of sample determination function on it successively in some cases.In use, be applied to sample on the exfoliated test specimen after, the strip off rete is so that observe the colour developing of reagent layer.
More particularly, can leach the particulate of whole blood and the rete of the appropriate amount sample of measuring the arrival reagent layer is superimposed on the reagent layer of being made by thermoplastic resin that soaks into reagent or non-thermal plasticity material matrix.When using such dry analysis kit, sample (whole blood) is applied on the rete, particulate and excessive blood are wiped the surface from rete, and the strip off rete, expose reagent layer so that observe the colour developing degree of reagent layer.In some cases, the following examination with wiping can the strip off rete.
As mentioned above, reagent layer directly being fixed to suprabasil the most frequently used method is to fix with double-faced adhesive tape.Yet double-faced adhesive tape uses acrylic resin usually, and contains and be not a spot of polymerization initiator, monomer, stabilizing agent, plastifier and wetting agent.These compositions when contacting, be tending towards with reagent layer with reagent layer in the reagent colour developing or the decomposition that react and cause active component.Therefore, need the strict double-faced adhesive tape of selecting for each project.
And, fixedly have defective like this with double-faced adhesive tape, i.e. bonding agent and processor adhesion can cause mechanical disorder, and with the reagent layer surface adhesion can make the part reagent layer not with example reaction, thereby cause color to form inequality.
In order to eliminate these defectives relevant with double-faced adhesive tape, available heat hot melt adhesive (containing the bonding agent at 80-150 ℃ of softening thermoplastic resin) is fixed.Yet in this case, whole reagent layer must down keep several seconds so that the melting heat hot melt adhesive at 100-110 ℃, and this can cause reagent, particularly the sex change of protein (for example enzyme, antibody and antigen).In addition, hot-melt adhesive and double-faced adhesive tape are similar, contain plastifier, stabilizing agent and similar substance thereof, and these components have harmful effect to reagent.
As disclosed among the JP-B-53-6551 (so used " JP-B " speech mean " the open Japanese patent application of examine), proposed already to be closed to reagent layer in fabric or the web and to use the hot-melt adhesive fusion to glue together the method on strip of paper used for sealing both sides a kind of comprising " as the solution of these prominent questions.This comprises and reagent layer is closed in the nylon wire and successfully solved above-mentioned two problems with the method that hot-melt adhesive glues together its both sides.Yet because the vibrations nylon wire becomes loose, the result causes reagent layer to be tending towards moving or coming off in transportation.In addition, this method is loaded down with trivial details and expensive.
Disclose a kind of preparation of compositions method that is used to detect among the JP-B-6-68488, this method comprises to be inserted thermoplastic resin between reagent layer and the substrate and by laser beam or ultrasound wave cutting thin layer so that by the fixing cutting zone of fusion.This technology can prepare the multilayer kit that is used for dry analysis, and need not to use bonding agent.Yet prepared kit is to clamp could be picked up or be put in use a type on the platform as the pole of handle.And, wasted by the edge of laser beam or ultrasound wave cutting-out.In addition, need to produce laser beam or hyperacoustic machine of the enough energy that are used to cut lamination, and this machine is normally expensive.
Particularly, being fixed to suprabasil reagent layer herein is glass fiber filter paper etc., it can will be used for utilizing antibody, antigen, the antibody-avidin-chemical glues such as biotin composite of the microanalysis of immune response (the so-called immunoassay of doing) to be incorporated into it, therefore use double-faced adhesive tape or hot-melt adhesive not only can cause the problems referred to above but also can cause other problem, be the material of unreacted component or influence reaction by non-specific absorption on glass fiber filter paper, thereby cause big error.
And because exfoliated test specimen comprises three layers at least, so preparation process becomes loaded down with trivial details because relating to two steps; One of them step is to be used for ground floor is adhered to the second layer, and its next step is to be used for adhering to the second layer with the 3rd layer.
In addition, when removing rete, must between rete and reagent layer, peel off.It is quite inconvenience that interface between substrate and reagent layer is peeled off test specimen.Consider this point, the adhesion strength between reagent layer and the substrate should be greater than the adhesion strength between reagent layer and the rete (after this being called " interlaminar strength ").And make two interlaminar strengths between the bonding interface variant is quite loaded down with trivial details.
Can once stacked adhesion three layers, utilize two kinds of bonding agents to make two interlaminar strengths between the bonding interface variant simultaneously.Yet as mentioned above, used composition is tending towards the reagent in the reagent layer is had harmful effect in the bonding agent.Therefore, it is unwelcome using bonding agent.
Therefore need a kind of Perfected process that is used to prepare exfoliated test specimen of exploitation, utilize this method just can once fix three layers, can also make the splitting bonding strength variant simultaneously without bonding agent.
Have found that can be following the problems referred to above in the preparation of solution dry analysis kit: can utilize thermoplastic resin as one of reagent layer and underboarding or both materials, and from the outside ultrasonic vibration and pressure are applied on the assembly of reagent layer and underboarding so that the generation heat of friction.
Summary of the invention
The used ultrasound wave fusion technology of the present invention has following advantage:
Different with the adhesion of being undertaken by bonding agent, the thermoplastic resin that constitutes one or several layer is to carry out fusion and fixing by the heat of friction that ultrasound wave produces.Therefore, the plastifier that can not be subjected to existing in the bonding agent of the reagent in the reagent layer or the influence of solvent.Because heat is in the surperficial instantaneous generation of layer and reduces rapidly, so the reagent in the reagent layer can sex change.
The method is economical; Because reagent layer and substrate directly are secured together, thereby need not to cut away the edge.Because the used ultrasonic vibration of the present invention directly is sent to reagent layer, therefore the ultrasonic generator that uses is more relatively cheap.
Be subjected to ultrasonication at the stratiform thing that constitutes from the one side by some thermoplastic resins or thermoplastic resin and non-thermal plasticity porous layer, thereby cause under the situation of ultrasonic fusion, the present inventor has found that, when the splitting bonding strength that compares between each interface, the interface is near more from being applied with hyperacoustic that side, and interlaminar strength is just big more.Of the present invention by finishing in the preparation that this principle is applied to exfoliated test specimen just.
When producing heat and heat directly being sent to three layers of a fusion of device gummed in several layers, though can be fixed from that the nearer interface of example that is applied with heat, wanting fixing with regard to the heat conduction is difficult from that side interface far away.Even can fix interface far away, nearer interface also will be damaged by bigger heat till that time, and reagent will be finished and lose activity.
On the contrary, the method according to this invention, heat is not directly but is transferred to indirectly in several layers.That is, ultrasonic vibration is sent in several layers so that produce heat of friction.The problems referred to above can not appear like this, just.
Therefore.The invention provides a kind of quite new method for preparing dry analysis kit and exfoliated test specimen, the method is those defectives relevant with conventional art not, have also effectively utilized all advantages of ultrasonic fusion simultaneously.
The purpose of this invention is to provide a kind of method that in the preparation of the dry analysis kit that is used for measuring the fluid sample special component, directly reagent layer is fixed on the underboarding, wherein at least one in reagent layer and the underboarding is thermoplastic resin, and this method comprises the steps:
Reagent layer is contacted with underboarding and be applied on two layers, thereby produce heat of friction, the surface of melting heat plastic resin thus from the outside with ultrasonic vibration and pressure;
Exert pressure so as the thermoplastic resin surface adhering that makes fusing to non-thermoplastic material or the thermoplastic layer surface is become one with underboarding; And
Cancellation ultrasonic vibration and pressure.
Description of drawings
Fig. 1 is the skeleton view according to dry analysis kit of the present invention, and this figure is common to embodiment 1,2 and 3, has finished the fixing of reagent layer and underboarding this moment.
Fig. 2 is according to the cross-sectional view of the dry analysis kit of embodiments of the invention 1, shows rigid condition.
Fig. 3 is according to the cross-sectional view of the dry analysis kit of embodiments of the invention 2, shows rigid condition.
Fig. 4 is the planimetric map of the dry analysis kit of example 1 of the present invention, and finished fixing this moment.
Fig. 5 is the cross-sectional view of the dry analysis kit of example 1 of the present invention, and finished fixing this moment.
Fig. 6 finishes planimetric map fixing and the dry analysis kit of the present invention afterwards of cutting into inch strips.
Fig. 7 is the planimetric map of a dry analysis kit, in this kit in the zone except that core by fusion fixating reagent layer.
In Fig. 1 to Fig. 7,
(1) ... the reagent layer of the reagent layer of embodiment 1 (porous matrix that coats or soak into reagent) or embodiment 3 (the extremely thin layer that coats with reagent)
(2) ... substrate (porous matrix that thermoplastic resin board or non-thermoplastic material are made)
(3) ... the melt portions of substrate (resin)
(4) ... the reagent layer of embodiment 2 (with the thermoplastic resin film of reagent coating)
(5) ... substrate (thermoplastic resin board)
(6) ... (4) and the melt portions of (5)
(7) ... fusion gummed part (line)
(8) ... fusion gummed part (point that does not comprise the reagent layer core)
Fig. 8 shows the planimetric map and the side view of dry analysis kit of state before cutting according to embodiments of the invention 3.
Fig. 9 is the planimetric map of dry analysis kit of state after cutting according to embodiments of the invention 3.
Figure 10 is the top amplification view of dry analysis kit shown in Figure 9.
In Fig. 8 to Figure 10,
(9) ... underboarding (substrate)
(10) ... reagent layer (extremely thin thermoplastic resin film)
(11) ... fusion gummed part
Figure 11 shows the planimetric map and the cross-sectional view of dry analysis kit of state before cutting according to embodiments of the invention 4.
Figure 12 is that the dry analysis kit with Figure 11 is cut into 7mm width (xsect and Figure 11 hardwood) planimetric map afterwards.
In Figure 11 to Figure 12,
(12) ... underboarding (substrate)
(13) ... reagent layer (porous matrix)
(14) ... rete
(15) ... ultrasonic fusion gummed part (line).
For easy to understand structure of the present invention, in these figure, suitably revised the ratio of width and thickness.
Embodiment
According to fixing means of the present invention various embodiment can be arranged.Utilize reference number that embodiment is described below with reference to the accompanying drawings.
Embodiment 1:
A kind of method that in the preparation of the dry analysis kit that is used for measuring the fluid sample special component reagent layer directly is fixed on the underboarding comprises the steps:
Reagent layer (1) is contacted with underboarding (2) and apply ultrasonic vibration and pressure, produce heat of friction thus so that the surface of the underboarding (2) that fusing contacts with reagent layer (1) or the surface of the reagent layer (1) that fusing contacts with underboarding (2) from the outside;
Exerting pressure, the melted surface material of one deck is adhered on another layer so that make wherein; And
Cancellation ultrasonic vibration and pressure.
In this embodiment, one of underboarding (2) and reagent layer (1) are made by thermoplastic resin, and another is the porous matrix that constitutes at thermoplastic.In other words, embodiment (1) comprises two types; In one type, underboarding (2) is a thermoplastic resin board, and reagent layer (1) is the porous matrix that is made of the non-thermoplastic material that coats with reagent or soak into; In another kind of type, underboarding (2) is the plate of being made by the porous matrix that non-thermoplastic material constitutes, and reagent layer (1) is the thermoplastic resin film that coats with reagent.
In another embodiment, described as the reference number of the accompanying drawing of following utilization, underboarding and reagent layer can all be made by thermoplastic resin.
Embodiment 2:
A kind of method that in the preparation of the dry analysis kit that is used for measuring the fluid sample special component reagent layer directly is fixed on the substrate comprises the steps:
Reagent layer (4) is contacted with substrate (5) and apply ultrasonic vibration and pressure from the outside, whereby the surface of the surperficial and reagent layer (4) that contacts with substrate (5) of the substrate (5) that contacts with reagent layer (4) of fusing so that produce heat of friction;
Exert pressure, the melted surface of substrate (5) and the melted surface of reagent layer (4) are become one; And
Cancellation ultrasonic vibration and pressure.
In this embodiment, all make as the substrate (5) and the reagent layer (4) of underboarding by thermoplastic resin.Reagent layer (4) has two kinds of forms; The i.e. porous matrix that soaks into or coat with reagent, and the thin resin film that coats with reagent.In Fig. 3, indicate the part that substrate (5) and reagent layer (4) are integrated with reference number (6).
One embodiment of the present of invention have been used and have been turned round ultrasound wave.
Embodiment 3:
A kind of reagent layer that will comprise the extremely thin thermoplastic resin film that coats with reagent in the preparation of the dry analysis kit that is used for measuring the fluid sample special component directly is fixed to the method on the substrate, comprises the steps:
Make reagent layer contact and apply and turn round ultrasonic vibration and external pressure, so that the reagent layer surface that fusing contacts with substrate with substrate;
Exert pressure so that make the melted surface of reagent layer be adhered on the substrate surface or the melted surface of reagent layer and substrate surface are integrated;
Ultrasonic vibration and pressure are turned round in cancellation.
Term used herein " is turned round ultrasound wave " and is meant the notion that has the transverse vibration characteristic mainly.The notion of representing with this term forms contrast with the notion of the used usually term that means vertical vibration " ultrasound wave ".
Make its sight that rotates a fixed position just be readily appreciated that the notion of " turning round ultrasound wave " this speech simultaneously to the flat board extruding vial (having annular mouth) mouth down by visual.The vial edge is equivalent to the loudspeaker of ultrasonic oscillator, and twisting motion is equivalent to transverse vibration.
Common vertical ultrasonic vibration can not be melted extremely thin thermoplastic resin film.On the other hand, the generation transverse vibration leads ultrasound wave because its fabulous energy efficiency can be sent to the surface of extremely thin film with vibrational energy so that melt this film.Because transverse vibration also has " fricting movement ", so the dry analysis kit to provide to have as the film of reagent layer in the substrate can be provided the complete fusion of extremely thin film for it.By " fricting movement ", even under the low condition of little energy, heat, turn round ultrasound wave and also the complete fusion of extremely thin film can be glued in the substrate.
Embodiment 4:
A kind of preparation is used for measuring the method for exfoliated test specimen of the dry analysis of fluid sample special component, this test specimen comprises a underboarding, have a reagent layer that constitutes by the porous matrix that soaks into reagent on the real base plate and have the tear-away rete that leaches the particle function, peel this tear-away rete so that observe the colour developing of reagent layer after applying sample, this preparation method comprises the steps:
Stacked successively reagent and rete and they are contacted with each other on underboarding apply ultrasonic vibration from underboarding one side then;
Exert pressure so as the surface adhering that makes melting zone to the surface of contiguous not melting zone or the surfacing of melting zone and the surface of adjacent layer are integrated; And
Cancellation ultrasonic vibration and pressure.
In the present invention, no matter substrate is to make with thermoplastic resin or with non-thermoplastic material, all should have such thickness to guarantee that having enough intensity supports the reagent layer that will be fixed to the upper.With decide this thickness for the identical mode of general dry analysis kit.Substrate thickness is generally 0.1 to 0.4mm.
Non-thermoplastic material comprises materials such as paper (filter paper), timber, adhesive-bonded fabric (such as film filter paper), yarn fabric, knitted fabric, glass (such as glass fiber filter paper), sinter, pottery (such as the vesicular potsherd), hardware cloth and the polymer particles of three-dimensional net structure.Preferably these materials are porous matrixes.Importantly do not answer the heating and melting material.
The thermoplastic resin that is used for underboarding or reagent layer can be selected from those materials that are generally used for this dry analysis kit.Preferred example is polyethylene terephthalate (being abbreviated as PET sometimes), polycarbonate, polypropylene, tygon, polystyrene, polyvinyl acetate, Polyvinylchloride and cellulosic acid.The form that these materials exist has such as uniaxial tension perforated membrane, biaxial stretch-formed perforated membrane and radiation perforated membrane.
The available method for preparing the dry analysis kit that adopts is traditionally finished with reagent and is soaked into or coated porous base makes and coats thermoplastic resin film with reagent.Promptly, to analyze required specified rate agent dissolves or be distributed in the solvent, by soaking into device etc. solution or dispersion liquid are infiltrated in the porous matrix then, reagent and solvent and polymer adhesive are mediated, be applied to potpourri on the film by coating unit at last and dry in exsiccator.
Make reagent layer and underboarding superimposed, and apply several 10
-1Ultrasonic vibration and the pressure of second.The frequency of ultrasonic vibration is 20KHz and pressure is 60-80kg/cm
2Comparatively desirable.Stop ultrasonic vibration and pressure lasting more other several 10
-1Second, remove pressure then.Like this, sample layer and underboarding just have been secured together.
All be subjected under the situation of ultrasonic fusion at all contact areas between reagent layer and the underboarding, still affacted on the reagent though some influences of melting heat are faint.Need not any precautionary measures and avoid though these influences are very faint, preferably reagent layer and substrate are not that fusion is glued together on the whole surface of reagent layer but on many points.This can be by for example only assigning to ultrasound wave to be avoided with outer peripheral portion rather than central part that point or line form are applied to reagent layer.The example of this some fusion as shown in Figure 7.The example of this line fusion as shown in Figure 4 and Figure 5.
For example can be prepared as follows the dry analysis kit of embodiment 1: with can by with fluid sample in the analyte generation specific reaction reagent that forms color soak into filter paper, the dry then filter paper that is soaked into, to obtain reagent layer, reagent layer is put into as also pressurization on the polyethylene terephthalate of underboarding, apply ultrasound wave simultaneously, the fusing polyethylene terephthalate at underboarding edge is adhered on the reagent layer by the mode that we are called braking effect thus, thereby has finished all fixing.
In the dry analysis kit of the another kind of type of embodiment 1, example can be prepared as follows reagent layer: with can with fluid sample in form the reagent of color during contained analyte generation specific reaction and the kneading potpourri of polymer adhesive coats polyethylene terephthalate, carry out drying thereafter and come the generate a reagent layer.Then reagent layer is placed in the substrate of making and applies ultrasound wave by non-thermal plasticity porous matrix (for example filter paper).The surface that is the reagent layer film contacts with the substrate of being melted by ultrasound wave.The polyethylene terephthalate of fusing is adhered on the underboarding by so-called braking effect, thereby has finished all fixing.
When the pet film that is generally used for this area was used to prepare reagent layer, its thickness was 50-150 μ m.
When being used for dipping systems, back a kind of dry analysis kit of embodiment 1 also has other advantage.That is, when being dipped into the dry analysis kit in the fluid sample and taking out, excessive fluid sample is absorbed by underboarding, thereby has avoided moving in the reagent layer.
For example can be prepared as follows the dry analysis kit of embodiment 2: with can with fluid sample in form the reagent of color during contained analyte generation specific reaction and the kneading potpourri of polymer adhesive coats pet film, secondly by dry generate a reagent layer, then reagent layer is placed on the polyethylene terephthalate plate and pressurization, applies ultrasound wave simultaneously.The fusing polyethylene terephthalate of reagent layer edge and basal edge comes in contact and is integrated.On a temperature spot, both are completely fixed together.
In embodiment 3, when using the underboarding of being made by thermoplastic resin, the molten resin of reagent layer is integrated with the underboarding resin of similarly ultrasound wave fusing, and therefore is secured together.When using the underboarding of being made by the non-thermoplastic material porous matrix, the molten resin of reagent layer enters in the hole of underboarding, thereby has finished fixing by so-called braking effect.
Make reagent thin layer and underboarding superimposed and apply several 10
-1Second turn round ultrasonic vibration and pressure.The frequency of turning round ultrasonic vibration is 40HKz and pressure is 60-80kg/cm
2Comparatively desirable.Next stops ultrasonic vibration and makes pressure continue several 10 again
-1Second, remove pressure then.Like this, reagent layer and underboarding just can be fixed together.
In addition, in embodiment 3, thermoplastic resin membrane's thickness is preferably 10-50 μ m.
In embodiment 4, when thermoplastic resin and the porous matrix of being made by non-thermoplastic material are adjacent one another are, pacing items is that resin that the thermoplastic resin on the preceding layer of surface part is melted and melt by ultrasound wave is forced in the bonding hole of advancing back one deck, fixes thereby finished by so-called braking effect.When two adjacent layers all are to be made and two-layer surface resin when being melted by thermoplastic resin, pacing items is two-layer surface resin integrator, thereby has finished fixing.
Therefore, utilize three the basic layers of porous matrix for formation as the exfoliated test specimen of reagent layer, importantly (1) three layer all is to be made by thermoplastic resin, (2) wherein two-layer is to be made by thermoplastic resin, all the other one decks are porous matrixes of being made by non-thermoplastic material, perhaps one deck is to be made by thermoplastic resin in the middle of (3), and upper and lower layer is the porous matrix of being made by non-thermoplastic material.In other words, it should be noted that the porous matrix of being made by non-thermoplastic material can not be adjacent with another porous matrix of being made by non-thermoplastic material.
In more detail, the porous matrix that utilizes of the present invention comprises following layer structure as the exfoliated test specimen of reagent layer.
(1) all underboarding, reagent layer and retes all are to be made by thermoplastic resin.
(2) underboarding and rete are made by thermoplastic resin, and reagent layer is the porous matrix of being made by non-thermoplastic material.
(3) underboarding and rete are the porous matrixes of being made by non-thermoplastic material, and reagent layer is the porous matrix of being made by thermoplastic.
(4) underboarding and reagent layer are made by thermoplastic resin, and rete is the porous matrix of being made by non-thermoplastic material.
Rete be one have many can filtering blood and the matrix in the hole of liquid hold-up.Can be selectively, rete itself does not have the hole but is furnished with one to have the parts of measuring sample or keeping sample ability.
Example to the method for the dry analysis kit that has the fixating reagent layer according to the present invention preparation and exfoliated test specimen describes below with reference to the accompanying drawings.Should be appreciated that and to think that therefore the present invention is restricted again.
Example 1
Prepare as an example according to following prescription and to be used for detecting the dry analysis kit that urine is occulted blood.
Prescription
First soaks into solution:
Potassium Hydrogen Phthalate 150ml
(0.5M；pH5.3)
Ethanol 100ml
Lauryl sodium sulfate 200mg
Disodium EDTA 20mg
Cumene hydroperoxide 20ml
Second soaks into solution:
Ethanol 80ml
Dimethylbenzene 120ml
7-methylquinoline 1ml
3,3 ', 5,5 '-tetramethyl benzidine 1g
Porous matrix: by the 2CHr filter paper of Whatman production
The PET film that substrate: 0.3mm is thick
Porous matrix is dipped into according to first soaking in the solution and dry that above-mentioned prescription is made, is dipped into second and then and soaks in the solution and dry, thereby obtain reagent layer.Be put into resulting reagent layer in the substrate and on it, apply ultrasonic vibration and the 70kg/cm that frequency is 20KHz
2Pressure, continued for 0.2 second.Stop ultrasonic vibration then and make pressure continue other 0.2 second again, remove pressure at last.
In this example, apply ultrasonic vibration with the line form.Melting condition as shown in Figure 4 and Figure 5.Have the porous matrix that reagent is fixed therein like this and be cut into the preset width of 5mm, thereby obtain dry analysis kit as shown in Figure 6.
Reference examples 1
In order to compare, will to utilize double-faced adhesive tape to be adhered in the substrate according to the reagent layer of the formulation identical and be cut into pre-sizing, thereby obtain the dry analysis kit with example 1.
Each dry analysis kit of above-mentioned preparation is put into vial and seal with drying agent.At 50 ℃ vial is preserved one section preset time so that carry out accelerated test.(0mg/dl is appointed as preparation 1 to two different hemoglobin levels that have that prepared in the past as sample to utilize special-purpose reflectance photometer (by the spectrally resolved tintmeter SZ-∑ 80 of Nippon Denshoku Kogyo k.K production); And 0.2mg/dl, be appointed as preparation 2) contrast urine preparation analyze.The result who obtains is shown in following table 1.
Table 1
Reflectance (R%)
| Hemoglobin level | |
| (preparation 1) 0mg/dl | (preparation 2) 0.2mg/dl |
| 0 | 7 | 14 | 0 | 7 | 14 | |
| Preserve fate ultrasound wave fusion double-faced adhesive tape | (initially) 97.4 97.8 | 96.0 89.2 | 94.5 81.8 | (initially) 19.0 18.8 | 20.8 35.7 | 22.2 48.2 |
Can see that from table 1 reflectance reduces in time in the analysis of preparation 1.The reducing of reflectance means that the color of reagent layer shoals, thereby shows the poor stability of reagent layer.As observed, the increase of the reflectance of preparation 2 means that the sensitivity of reagent layer reduces, thereby also shows the poor stability of reagent layer.Result in the table 1 confirms: have obvious improvement by the dry analysis kit that ultrasound wave fusion technique for fixing prepares according to the present invention aspect stable.
Stability reduction is to cause that by the influence such as organic solvent and these compositions of plastifier contained in the double-faced adhesive tape they can make the analysed composition instability.On the contrary, the influence that can not be subjected to these compositions by the fixing reagent layer of ultrasound wave fusion is not subjected to the influence of fusion heating yet.
Reference examples 2
In order to check the influence degree of fixing heating, utilize the mode identical to prepare reagent layer and cut into inch strips but be not fixed to be prepared into a dry analysis kit on the underboarding and it is being compared under whole situations about contacting between reagent layer and the underboarding with dry analysis kit of the present invention with example 1.By special reflectance photometer the contrast urine preparation with 0.2mg/dl hemoglobin level as the former preparation of sample is analyzed.Carry out 5 times for each dry analysis kit and measure, resulting result is shown in following table 2.
Table 2
Reflectance (R%)
| |
||||||
| 1 | 2 | 3 | 4 | 5 | Mean value | |
| The dry analysis kit of ultrasound wave fusion does not have the dry analysis kit of underboarding | 19.5 18.3 | 20.2 16.8 | 18.5 19.2 | 17.3 18.9 | 19.5 19.3 | 19.0 18.5 |
Can see that from table 2 result who is obtained by the dry analysis kit of ultrasound wave fusion preparation is basic identical with the result of the dry analysis kit that does not have underboarding under reagent layer and situation that underboarding all contact, thereby confirmation almost there is not hot influence according to ultrasound wave fusion of the present invention to reagent.
Example 2
The dry analysis kit that is used for detecting the urine nitrite according to following prescription as an example preparation.
Prescription
D-naphthylamines 1.0g
Sulfanilamide (SN) 2.5g
Trichloroacetic acid 3.0g
Tygon butyl acetal 20.0g
Methyl alcohol 100ml
Thermoplastic resin board (as underboarding (9) ... the PET film that 0.3mm is thick)
Thermoplastic resin film (as reagent layer (10) ... the PET film band that 1cm is wide, 20 μ m are thick)
Ultrasonic oscillator ... by the 900Series that Emerson japan Ltd produces, Model947M
Be applied on the film according to above-mentioned formulation coating composition and with coating machine, thickness reaches 400 μ m, and is dry in hot-air then, thereby be prepared into reagent layer (reagent layer (10)).
With reagent layer (10) be placed on substrate (9) go up and on it, apply frequency be 40HKz turn round ultrasonic vibration and 70kg/cm
2Pressure, continued for 0.2 second.Stop vibration, make pressure continue other 0.2 second again, remove pressure then.
The loudspeaker of used ultrasonic generator are that an external diameter is that 6mm, internal diameter are the cylindrical of 4mm.Indicated as reference number among Fig. 8 to Figure 10, thereby fixing by fusion in the annulus of its outer peripheral portion, reagent layer avoided part therein to fix.The external diameter of annulus is that 6mm, internal diameter are 4mm.
The dry analysis kit of preparation like this shown in Figure 8 is cut into the wide bar of 1cm, thereby obtains dry analysis agent box shown in Figure 9.
When the dry analysis kit being dipped in the urine that contains nitrite, can obtain satisfactorily and the corresponding redness of content of nitrite.
Use under the situation of extremely thin film as reagent layer the above-mentioned example resembling, common ultrasound wave can not produce fusion, can produce fusion as mentioned above with preparation dry analysis degree agent box and actively do not descend and turn round ultrasound wave.
Example 3
Prepare exfoliated test specimen according to following technology as an example.Substrate (underboarding):
0.3mm thick white polyethylene terephthalate film,
Produce (shown in reference number among Figure 11 (12)) porous matrix (reagent layer) by Teijin Ltd.:
0.3mm thick filter paper, the 3MMchr that produces by Whatman (rete shown in reference number among Figure 11 (13):
0.3mm thick nylon wire is produced (shown in reference number among Figure 11 (14)) by Teijin Ltd.
The wide rete band of reagent layer band that 7mm is wide and 10mm is placed in the substrate of 70mm * 360mm according to the order of describing as shown in figure 11.With frequency is ultrasonic vibration and the 70kg/cm of 20KHz
2Pressure be applied to a side of substrate, continued for 0.2 second, stop after the ultrasonic vibration, make pressure continue other 0.2 second again, remove pressure then.Apply ultrasound wave and pressure with the line form.Fixed part is shown in the reference number among Fig. 1 l (15).After this, it is wide that fixed bed is cut into 7mm, thereby obtain exfoliated test specimen shown in Figure 12.
Test:
Prepare 20 test specimens.With the rete of 10 μ l blue inks (the moisture ink that is used for pen) each test specimen of drop, wipe examination after the drop at once.After 60 seconds, peel off sample determination layer (rete).
The result:
All reagent layers of finding 20 test specimens all show blue.When removing rete, the neither one test specimen is that the interface between underboarding and reagent layer is peeled off, and all is that interface between rete and reagent layer is peeled off.
Because method of the present invention is not used bonding agent (double-faced adhesive tape, hotmelt etc.), therefore reagent is not had chemical affect, and on performance, make moderate progress yet.Reagent can not be subjected to the physical damage that the adhesive effect owing to paste adhesive etc. causes yet.Do not use bonding agent that cost is descended.From the angle of production equipment, because can use cheap ultrasonic generator, so machine is simpler and cheap, and related step also oversimplified, and production cost is reduced.
In addition, even when the so thin film that common ultrasonic energy can not be concentrated during as reagent layer, method of the present invention also can be carried out ultrasonic fusion safely and reliably.
And the present invention is as described in detail, can once fix three layers and need not by bonding agent, can be given in twos between the interface difference on interlaminar strength simultaneously to prepare exfoliated test specimen.That is, the invention provides a kind of method of the quite new exfoliated test specimen of preparation, this method is those defectives relevant with conventional art not, and have effectively utilized whole advantages of ultrasonic fusion.
When describing the present invention with reference to specific examples of the present invention, various variations of being done in not breaking away from marrow of the present invention and scope and modification all are conspicuous for the person of ordinary skill of the art.
Claims (8)
1. method for preparing the exfoliated test specimen of the dry analysis that is used for measuring the fluid sample special component, this test specimen comprises a underboarding, a reagent layer, with a tear-away rete, wherein, described reagent layer has the porous matrix that soaks into reagent, and place on the described underboarding, and described tear-away rete has the effect that leaches particle, and place on the described reagent, after applying sample, peel described tear-away rete to observe the colour developing of reagent layer, wherein, described underboarding, described reagent layer and described tear-away rete are the porous matrixes of being made or being made by non-thermoplastic material by thermoplastic resin, arrange in such a way: the porous matrix layer of being made by non-thermoplastic material is not adjacent with another porous matrix layer of being made by non-thermoplastic material, and melt described underboarding by applying ultrasonic vibration or pressure, in described reagent layer and the described tear-away rete at least one, described preparation method comprises the steps:
Described reagent layer and tear-away rete are contacted with each other be stacked on the underboarding and and apply ultrasonic vibration from underboarding one side by this order;
Exert pressure so that on the surface of the adjacent non-melt layer in the surface adhering one described underboarding of the melting zone in described underboarding, described reagent layer and the described tear-away rete, described reagent layer and the described tear-away rete, or the surfacing of the melting zone in described underboarding, described reagent layer and the described tear-away rete and the surface of adjacent layer are integrated; And cancellation ultrasonic vibration and pressure.
2. the method for claim 1 is characterized in that described tear-away rete has a plurality of holes and itself has the ability of filtering blood, or the ability of liquid hold-up, and is furnished with the parts with measuring samples or keeping sample ability.
3. the method for claim 1 is characterized in that described thermoplastic resin selects from polyethylene terephthalate, polycarbonate, polypropylene, tygon, polystyrene, polyvinyl acetate, Polyvinylchloride or cellulose esters.
As right according to 1 described method, it is characterized in that from timber, non-woven, textile, knitted fabric, glass, sinter, pottery, hardware cloth and polymer particles, selecting by the described porous matrix that non-thermoplastic material is made.
5. method for preparing the exfoliated test specimen of the dry analysis that is used for measuring the fluid sample special component, this test specimen comprises underboarding, a reagent layer, with a tear-away rete, wherein, described reagent layer has the porous matrix with reagent-impregnated, and place on the described underboarding, and described tear-away rete has the effect that leaches particle, and place on the described reagent, after applying sample, peel of the colour developing of described tear-away rete with the observation reagent layer, underboarding wherein, reagent layer and tear-away rete glue together mutually with the line form, or glue together mutually at a plurality of discrete points, wherein, described substrate version, described reagent layer and described tear-away rete are made by thermoplastic resin or are made by the porous matrix that non-thermoplastic material is formed, arrange in such a way: the porous matrix layer of being made by non-thermoplastic material is not adjacent with another porous matrix layer of being made by non-thermoplastic material, and melt described underboarding by applying ultrasonic vibration or pressure, in described reagent layer and the described tear-away rete at least one, described preparation method comprises the steps:
Make described reagent layer and the rete that comes off contacts with each other to be stacked on the underboarding and from underboarding one side by this order and applies ultrasonic vibration;
Exert pressure so that the surface of the melting zone in described underboarding, described reagent layer and the described tear-away rete is invaded and be glued on the surface of the adjacent non-melt layer in described underboarding, described reagent layer and the described tear-away rete with the line form or on a plurality of discrete points or the surfacing that makes the melting zone in described underboarding, described reagent layer and the described tear-away rete is integrated with the surface of adjacent layer with the line form or on a plurality of discrete points; And
Cancellation ultrasonic vibration and pressure.
6. method as claimed in claim 5 is characterized in that described tear-away rete has a plurality of holes and itself has the ability of filtering blood, or the ability of liquid hold-up, and is furnished with the parts with measuring samples or keeping sample ability.
7. method as claimed in claim 5 is characterized in that described thermoplastic resin selects from polyethylene terephthalate, polycarbonate, polypropylene, tygon, polystyrene, polyvinyl acetate, Polyvinylchloride or cellulose esters.
8. method as claimed in claim 5 is characterized in that being selected from timber, non-woven, textile, knitted fabric, glass, sinter, pottery, hardware cloth and polymer particles by the described porous matrix that non-thermoplastic material is made.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02156182 CN1250968C (en) | 1996-02-29 | 1996-02-29 | Reagent layer ultrasonic direct fixture and method for preparing stirpping test-piece |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02156182 CN1250968C (en) | 1996-02-29 | 1996-02-29 | Reagent layer ultrasonic direct fixture and method for preparing stirpping test-piece |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 96106074 Division CN1113242C (en) | 1996-02-29 | 1996-02-29 | Ultrasonic direct fixing of reagent layer and method for preparing peel type test piece |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1515908A CN1515908A (en) | 2004-07-28 |
| CN1250968C true CN1250968C (en) | 2006-04-12 |
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ID=34236138
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02156182 Expired - Fee Related CN1250968C (en) | 1996-02-29 | 1996-02-29 | Reagent layer ultrasonic direct fixture and method for preparing stirpping test-piece |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1250968C (en) |
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1996
- 1996-02-29 CN CN 02156182 patent/CN1250968C/en not_active Expired - Fee Related
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| Publication number | Publication date |
|---|---|
| CN1515908A (en) | 2004-07-28 |
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