CN1774628A - Analyzing tool being reduced in distance of diffusion of reagent and method for manufacture thereof - Google Patents
Analyzing tool being reduced in distance of diffusion of reagent and method for manufacture thereof Download PDFInfo
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- CN1774628A CN1774628A CN200480010320.XA CN200480010320A CN1774628A CN 1774628 A CN1774628 A CN 1774628A CN 200480010320 A CN200480010320 A CN 200480010320A CN 1774628 A CN1774628 A CN 1774628A
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Abstract
An analyzing tool (X1) which has a reaction space (4) for reacting a specific component in a sample with a reagent, and a reagent section (51, 52) being arranged in the reaction space (4) and being dissolved when the sample is supplied to the reaction space (4), wherein the reagent section (51, 52) comprises a first portion (51) and a second portion (52) which are opposed to each other in the face specifying the reaction space (4).
Description
Technical field
Employed analyzer is with its manufacture method when the present invention relates to the special component in analysis specimen.
Background technology
As employed analyzer by colorimetric and when measuring blood glucose value, glucose sensor shown in Figure 20 9 is for example arranged.This glucose sensor 9 has the form that engages first and second sheet material 91,92 by a pair of dividing plate 93.This glucose sensor 9 has the kapillary 94 by above-mentioned each member 91～93 regulation.Has reagent portion 95 in the inside of kapillary 94.This reagent portion 95 is when being supplied to blood and dissolve, and it is as containing the composition of reacted constituents such as colour former, oxidoreducing enzyme and electron transport substance and constituting.
In this glucose sensor 9,,, the blood that imports kapillary 94 is moved to opening 97 by the capillary force that the inside at kapillary 94 produces when importing under the situation of blood by opening 96.At this moment, in the inside of kapillary 94, the dissolving by reagent portion 95 constitutes the liquid-phase reaction system that contains glucose and reacted constituent.
In liquid-phase reaction system, be included in reacted constituent and the glucose diffusion in the reagent portion 95 and react, the electronics from glucose takes out for example is fed into colour former by electron transport substance.Color development is colored liquid-phase reaction system by this color development to colour former by being supplied to electronics.Coloring degree detects by optical means, predicts the result according to this, can calculate blood glucose value.
As mentioned above, in order to make the colour former color development, need at least to take out the reaction of electronics and the electronics that takes out is supplied to the reaction of colour former from glucose.On the other hand, in liquid-phase reaction system,, in liquid-phase reaction system, need dispersion equably to be included in the reacted constituent of reagent portion 95 in order to make the colour former color development expeditiously, to shorten minute.Yet, under the situation that reagent portion 95 constitutes as the composition that dissolves by the supply of test portion, after the higher state of the concentration of the reacted constituent that (part of reagent portion 95 is set) partly, change diffusion in time by reacted constituent, make the concentration of reacted constituent by homogenising gradually.Like this, in the concentration determination of carrying out with glucose sensor 9, exist minute to depend on the diffusible tendency of reacted constituent.In addition, in the initial stage that blood is imported kapillary 94, glucose with uniform concentration and existing roughly, but is accompanied by the carrying out of reaction in liquid-phase reaction system, glucose is consumed, and the concentration of unreacted glucose is at the high part step-down of the concentration of reacted constituent.Like this, reacted constituent not only is even the diffusivity of the CONCENTRATION DISTRIBUTION of concentration of glucose and even glucose also influences minute.
In glucose sensor 9, only on second clear sheet 92, form reagent portion 95, usually, the distance H between first clear sheet 91 and second clear sheet 92 is set in below the 200 μ m.Like this, in liquid-phase reaction system, in order to make the concentration homogenising of the reacted constituent that is included in reagent portion 95, and make the diffusion length of target component bigger.Certainly, the diffusion length of glucose also increases.There is such problem in its result in glucose sensor 9, that is: be used for obtaining as the time of goal response state (liquid-phase reaction system painted) longer, and minute is elongated.In this case, if set minute shortly, then under the situation of the concentration determination of carrying out the high blood of concentration of glucose, can not obtain in order to carry out the required sufficient color development of correct concentration determination, in the mensuration precision reduction of area with high mercury.On the other hand, if guarantee minute on one side shortly, Yi Bian guarantee to measure precision fully, then measurement range diminishes.
In addition, as electron transport substance, reagent portion 95 is contained under the situation of the unstable reagent such just like methoxy-PMS (reactive high reagent), when preserving glucose sensor 9, this unsettled reagent and other reagents reaction can produce the such unfavorable condition of error at measurment.Therefore, in that single reagent portion mixing is existed under the situation of multiple reagent,, measure precision and worsen because the various combination of these reagents keeps poor stability
Summary of the invention
The object of the invention is to provide a kind of can shorten analysis time, in addition, even also can analyze accurately at area with high mercury, and the analyzer of maintenance excellent in stability.
The analyzer that provides according to a first aspect of the invention, comprise and be used for making the special component of test portion and the reaction compartment of reagent reaction, with be configured in described reaction compartment and when test portion is supplied to described reaction compartment and the analyzer of the reagent portion of dissolving, wherein, described reagent portion has first relative and second portion mutually on the predetermined surface of the described reaction compartment of regulation.
First and second portion preferably as being formed by the member of mutually disjunction.Wherein, first and second portion also can be used as continuous members and form.
The composition of first and the composition of second portion are preferably different.Therefore, will be when preserving etc. easily the reagent of reaction give first and second portion, can make them not mix existence.Like this, the reaction each other of the reagent in the time of can suppressing to preserve improves storage stability.But, about the reagent of the reacting to each other property shortage when preserving, also can make its mixing be present in first and second portion in same section.
Analyzer of the present invention for example constitutes like this, by making reagent portion contain the color development reagent, and can carry out assaying by colorimetric that is:.Certainly, the present invention also goes for being undertaken by the electrode method analyzer of this formation of assaying, and in this case, reagent portion does not need to constitute as containing the part of color development reagent.
Predetermined surface for example comprises the first area that is provided with first and is provided with second portion and at the normal direction of the first area second area relative with the first area.In this case, the opposite of first area and second area is apart from preferably setting below 300 μ m.
The opposite is more preferably below 150 μ m apart from preferably setting below 200 μ m.The opposite distance for example is set in more than the 30 μ m.This is because under the irrelevantly little situation of distance, test portion comprises under the such situation of solid constituent at test portion as the blood that contains blood cell over there, perhaps under the big situation of the viscosity of test portion, can not successfully carry out the moving of test portion in the stream.
Analyzer of the present invention for example constitutes like this, comprising: have first sheet material of first area and have second area and and second sheet material of the first sheet material joint provisions reaction compartment.Analyzer of the present invention also can constitute like this, that is: comprise engaging first sheet material and second sheet material and and the dividing plate of these sheet material joint provisions reaction compartments.In this case, the opposite distance can be by the dividing plate defined.
Reaction compartment for example constitutes like this, that is: by the capillary force that produces at this reaction compartment test portion is moved.Wherein, also can utilize power such as pump that test portion is moved, in addition, analyzer of the present invention may not move it such structure at reaction compartment.
A second aspect of the present invention, a kind of manufacture method of analyzer is provided, comprise: form operation in the first reagent portion that forms the first reagent portion more than on first substrate, the second reagent portion that forms the second reagent portion more than on second substrate form operation and make the first and second reagent portion engage one another relative to each other first and second substrate, form operation with the intermediate that forms intermediate.
Here, on " first substrate " and " second substrate ",, also comprise and set a plurality of zones that become these sheet materials except the part of first and second sheet material in the analyzer that is equivalent to relate to a first aspect of the present invention.
Preferably form in the operation, first substrate is formed a plurality of first reagent portions, on the other hand, form in the operation, second substrate is formed a plurality of second reagent portions in the second reagent portion in the first reagent portion.In this case, manufacture method of the present invention preferably also comprises in order at least respectively to contain one first and the second reagent portion and cuts off the cut-out operation of intermediate.
The first reagent portion and the second reagent portion for example form as forming mutually different part.Like this, can provide the high reagent of a kind of separating reaction and with the easy analyzer of the reagent of reaction of this reagent.But, the first reagent portion and the second reagent portion also can form identical or roughly the same composition.
In manufacture method of the present invention, preferably also comprise: that carry out and in first and second substrate form on the face of the first or second reagent portion at least one before intermediate forms operation, keep the operation of dividing plate.This operation was preferably carried out before forming the first and second reagent portion on first and second substrate.Like this, can form the zone of reagent portion, in addition, can be suppressed at the part that forms reagent portion and keep the such unfavorable condition of dividing plate by the dividing plate regulation.Wherein, this operation also can be carried out after forming the first and second reagent portion.
As dividing plate, for example use on two-sided to have close-burning double sticky tape.Therefore, owing to do not need to the dividing plate or the first and second coating of substrates cementing agents, so, can improve the manufacturing efficient of analyzer.
A third aspect of the present invention, comprise the reaction compartment that is used for making the special component that is included in test portion and reagent to react, and the colorimetric analysis apparatus that by the described special component of colorimetric analysis the time, utilizes, a kind of like this analyzer is provided, that is: the predetermined surface of stipulating described reaction compartment comprises: the reagent retaining zone that is used to keep reagent, the zone, opposite that relatively has and do not keep reagent with normal direction and described reagent retaining zone in described reagent retaining zone, wherein, the opposite distance setting in described reagent retaining zone and zone, described opposite is below the 150 μ m.
Preferably be below the 100 μ m with the opposite distance setting, more preferably being set is below the 75 μ m.But, the opposite distance for example is set at more than the 30 μ m.This be because: under the irrelevantly little situation of distance, test portion comprises under the such situation of solid constituent at test portion as the blood that contains blood cell over there, perhaps under the bigger situation of the viscosity of test portion, can not successfully carry out the moving of test portion in the stream.
Reaction compartment for example constitutes like this, that is: test portion is moved.Can carry out like this for moving of test portion, that is: produce capillary force at this reaction compartment, utilize this capillary force to carry out.Certainly, also can utilize the power of pump to make the test portion of reaction compartment move such formation.
Analyzer of the present invention for example constitutes as such apparatus, comprising: have first sheet material of reagent retaining zone and have opposite zone and and second sheet material of the first sheet material joint provisions reaction compartment.Analyzer of the present invention for example also can be used as such apparatus and constitutes, and comprising: engage first sheet material and second sheet material and and the dividing plate of these sheet material joint provisions reaction compartments; In this case, the opposite distance can be by the dividing plate defined.
The present invention is applicable to the analyzer that for example uses blood as test portion.Certainly, the present invention also goes for using as test portion for example analyzer of urine beyond the blood.
Among the present invention, " opposite " this term, if be not particularly limited, it is as the state that not only comprises between the plane, also comprises the term of the state of plane and curved surface and the state between the curved surface and uses.In addition, so-called " opposite distance ", the meaning are meant in reagent during from the reagent retaining zone along its normal direction diffusion, arrive the greatest measure of zone, opposite required separation distance.
Description of drawings
Fig. 1 is the overall perspective view that expression relates to the glucose sensor of first embodiment of the invention.
Fig. 2 is the sectional view along the II-II line of Fig. 1.
Fig. 3 is the sectional view along the III-III line of Fig. 1.
Fig. 4 A and Fig. 4 B are the sectional views that is equivalent to Fig. 3 of travel condition that is used for illustrating the blood of kapillary.
Fig. 5 is the overall perspective view of employed substrate in the manufacture method of glucose sensor of Fig. 1～shown in Figure 3.
Fig. 6 is illustrated in the overall perspective view of pasting the state of double sticky tape on the substrate shown in Figure 5.
Fig. 7 be illustrated in be formed with a plurality of reagent portion on the substrate of state shown in Figure 6 the first time intermediate overall perspective view.
Fig. 8 is that expression engages two overall perspective view of the operation of intermediate for the first time.
Fig. 9 A～Fig. 9 D is the sectional view that expression relates to other modes of glucose sensor of the present invention.
Figure 10 A blocks the stereographic map that the part of other modes that relate to glucose sensor of the present invention is represented, Figure 10 B is its sectional view.
Figure 11 is the overall perspective view that expression relates to the glucose sensor of second embodiment of the invention.
Figure 12 is the sectional view along the XII-XII line of Figure 11.
Figure 13 is the sectional view along the XIII-XIII line of Figure 11.
Figure 14 A and Figure 14 B are the sectional views that is equivalent to Figure 13 of travel condition that is used for illustrating the blood of kapillary.
Figure 15 A blocks the stereographic map that the part of other modes that relate to glucose sensor of the present invention is represented, Figure 15 B is its sectional view.
Figure 16 A blocks the stereographic map that the part of the another way that relates to glucose sensor of the present invention is represented, Figure 16 B is its sectional view.
Figure 17 A blocks the stereographic map that the part of a mode again that relates to glucose sensor of the present invention is represented, Figure 17 B is its sectional view.
Figure 18 A～Figure 18 C is the chart of the measurement result of lasting variation of the absorbance in first embodiment.
Figure 19 A～Figure 19 C is the chart of the measurement result of lasting variation of the absorbance in second embodiment.
Figure 20 is the overall perspective view that is used to illustrate existing glucose sensor.
Embodiment
About preferred implementation of the present invention,, describe particularly with reference to accompanying drawing as first embodiment and second embodiment.
First embodiment
At first, first embodiment of the present invention is described.
Fig. 1～glucose sensor X1 shown in Figure 3 constitutes as Bullet structure, constitutes by colorimetric and measure concentration of glucose.This glucose sensor X1 has the form that engages first and second sheet material 1,2 of rectangle by a pair of dividing plate 3.This glucose sensor X1 has the kapillary of being stipulated by each member 1～3 4.
First and second sheet material 1,2 for example forms transparent by PET, PMMA, vinylon.On these sheet materials 1,2, under the state of the inside that is contained in kapillary 4 and be provided with the first and second reagent portion 51,52.Each reagent portion 51,52 constitutes like this, that is: form with respect to blood and the solid shape of dissolving easily, and at least one in these reagent portions 51,52 contains colour former.Therefore, blood being imported under the situation of kapillary 4,, be built into the liquid-phase reaction system that contains glucose and colour former in the inside of kapillary 4.
As colour former, can use well-known various product, but the preferred product that staggers from the absorbing wavelength of blood when the absorbing wavelength during color development by electronics acceptance that uses.As colour former, for example can use MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide).
First and the second reagent portion 51,52 also can be used as the member that contains electron transport substance or oxidoreducing enzyme and constitutes.Therefore, owing to the electronics that can carry out between glucose and the colour former is is more apace given and accepted, so can shorten minute.
As oxidoreducing enzyme, for example can use glucose dehydrogenase (GDH) or glucose oxidase (GOD), typically use PQQGDH.As electron transport substance, for example can use [Ru (NH
3)
6] Cl
3, K
3[Fe (CN)
6] or methoxy-PMS (5-methylphenazinium methylsulfate).
The composition of the first and second reagent portion 51,52 both can be identical, also can be different.But, under the situation of using the unsettled reagent (reactive high reagent) as methoxy-PMS, preferably this reagent is separated with other reagents, for example, in the first reagent portion 51, contain unsettled reagent, in the second reagent portion 52, contain other reagents.
A pair of dividing plate 3 is used to stipulate the distance between first and second sheet material 1,2, i.e. the width dimensions W of the height dimension H of kapillary 4, and regulation kapillary 4.In glucose sensor X1, a pair of dividing plate 3 separates certain intervals and disposes, and this becomes the width dimensions W of kapillary 4 at interval.On the other hand, the gauge of each dividing plate 3 is corresponding with the height dimension H of kapillary 4.
The inside of kapillary 4 is communicated with by opening 40,41.Opening 40 is used for blood is imported to the inside of kapillary 4, and opening 41 is used to discharge the inner air of kapillary 4.For this kapillary 4, the capillary force by the inside at kapillary 4 produces makes blood move in the inside of kapillary 4.
The width dimensions W of kapillary 4 for example is set at 0.05～10mm, the height dimension H of kapillary 4 (opposite distance) for example is set at below 30 μ m～1mm.Preferably the height dimension H with kapillary 4 is set at 300 μ m, is more preferably below the 200 μ m.
In glucose sensor X1, when supplying with under the situation of blood to kapillary 4 by opening 40, shown in Fig. 4 A and Fig. 4 B, the capillary force by producing in kapillary 4 makes blood advance in the inside of kapillary 4.In the traveling process of blood, reagent portion 51,52 is built into liquid-phase reaction system 42 by blood dissolves in the inside of kapillary 4.Being traveling in when blood arrives opening 41 of blood stops.
In liquid-phase reaction system 42, the electronics that takes out from glucose is supplied to colour former, thereby colour former is added lustre to, and liquid-phase reaction system 42 is colored.When in the first and second reagent portion 51,52, containing under the situation of oxidoreducing enzyme or electron transport substance, glucose generation idiosyncrasy in oxidoreducing enzyme and the blood, electronics is removed from glucose, after this electronics is supplied to electron transport substance, and is supplied to colour former.Therefore, the color development degree of colour former (coloring degree of liquid-phase reaction system) with the electron amount that takes out from glucose, be that concentration of glucose is relevant.
The coloring degree of liquid-phase reaction system 42, at this moment, is accepted to see through liquid-phase reaction system 42 and is penetrated light from second sheet material 2 that is: by 1 pair of liquid-phase reaction system 42 irradiates light of first sheet material for example by measuring like this.For the light that is radiated on the liquid-phase reaction system 42, employing be the light that manifests the bigger wavelength of absorption in the look of colour former.Final concentration of glucose can and see through generating through light intensity of liquid-phase reaction system 42 according to the incident light intensity of injecting liquid-phase reaction system 42.
In glucose sensor X1, face one another for making the first and second reagent portion 51,52, be divided into first and second sheet material 1,2 and form.Therefore, about the short transverse in the kapillary 4, for the concentration of homogenising colour former, the diffusion length of the colour former that needs is dwindled.
That is, when forming under the situation of reagent portion in first and second sheet material 1,2 only, if do not make colour former be diffused into the surface of the sheet material that is not formed with reagent portion, concentration that just can not the homogenising colour former.In contrast, when on first and second sheet material 1,2, not forming under the situation of reagent portion 51,52, the stage that begins to dissolve in reagent portion 51,52, because the concentration at the lip-deep colour former of each sheet material increases, concentration in the middle of them reduces, for the concentration of homogenising colour former, the centre that makes colour former be diffused into first and second sheet material 1,2 gets final product.Like this, when on two first and second sheet material 1,2, forming under the situation of reagent portion 51,52,, compare, become half with the situation that only on a sheet material, forms reagent portion for the diffusion length of the needed colour former of concentration homogenising that makes colour former.
This just means, when forming on first and second sheet material 1,2 under the situation of the first and second reagent portion 51,52, in liquid-phase reaction system, disperses the needed time of colour former to shorten equably, thereby can shorten the reaction time.
On the other hand, if be conceived to glucose, so, before reaction, the concentration of the unreacted glucose in the liquid-phase reaction system is roughly even, if but reaction proceeds to a certain degree, about the big zone of the concentration of colour former, the concentration of unreacted glucose reduces, in contrast, about the little zone of the concentration of colour former, the concentration of unreacted glucose increases.Therefore, in order to shorten minute, preferably in liquid-phase reaction system,, it is spread make the concentration homogenising even be not only the unreacted glucose of colour former.At this moment, as glucose sensor X1, if form the first and second reagent portion 51,52 on first and second sheet material 1,2, according to the reason same with colour former, the diffusion length of the needed unreacted glucose of homogenising concentration shortens.Put from this, also we can say, just can shorten the reaction time if on first and second sheet material 1,2, form the first and second reagent portion 51,52.
In addition, in glucose sensor X1, also can be clear and definite from the aftermentioned embodiment, by the opposite distance H being set at below the 300 μ m, can further shorten minute.That is,, make, on short transverse, diminish for the needed diffusion length of the concentration of homogenising colour former or unreacted glucose by dwindling the opposite distance H.Its result in glucose sensor X1, takes place easily in order to make the needed reaction of colour former color development, and the time that is used for obtaining reaching goal response state (liquid-phase reaction system painted) shortens, and makes that shortening minute becomes possibility.
Below, the manufacture method of glucose sensor X1 is described with reference to Fig. 5～Fig. 8.
As shown in Figure 5, (during with reference to Fig. 1～Fig. 3), at first prepare transparency carrier 6 making glucose sensor X1.Be set with on this transparency carrier 6 mutually perpendicular side upwardly extending a plurality of first and second and cut off line 61,62, the zone that is surrounded by these cut-out lines 61,62 forms zone 63 as glucose sensor.
Then, as shown in Figure 6, first cut off line 61, separate certain intervals and be pasted with a plurality of double sticky tapes 64 in order to cover each.Then, as shown in Figure 7, form the zone at each glucose sensor and be formed with reagent portion 65 on 63, thereby make intermediate 66 for the first time.Each reagent portion 65 has been for example by after having applied the reagent liquid that comprises colour former, oxidoreducing enzyme and electron transport substance, blows dry reagent liquid and forms.
Similarly, through the step with reference to Fig. 5～Fig. 7 explanation, make an intermediate 66 for the first time again, as shown in Figure 8, intermediate 66 for the first time engages one another.At this moment, make each for the first time the reagent portion 65 of intermediate 66 face mutually, utilize the clinging power of double sticky tape 64 to engage intermediate 66 for the first time, make intermediate (diagram slightly) for the second time.At last, cut off intermediate for the second time by cutting off line 61,62, and obtain Fig. 1～glucose sensor X1 shown in Figure 3 along first and second.
Relate to the form that glucose sensor of the present invention is not limited to illustrate in the present embodiment, for example also can make the such structure shown in Fig. 9 A～Fig. 9 D, Figure 10 A and Figure 10 B.
Glucose sensor X2 shown in Fig. 9 A is formed with first 51A of reagent portion on the first sheet material 1A, on the other hand, being formed with the cross section on the second sheet material 2A is the recess 20A of rectangle, forms second 52A of reagent portion in the inside of this recess 20A.In this glucose sensor X2, the opposite distance H is the bottom of recess 20A and the distance between the first sheet material 1A.
Glucose sensor X3 makes semicircle shape with the cross sectional shape of kapillary 4B shown in Fig. 9 B.More particularly, in glucose sensor X3, forming the cross section on the second sheet material 2A is the recess 20B of semicircle, forms second 52B of reagent portion in the inside of this recess 20B.In glucose sensor X3, the opposite distance H is the deep of recess 20B and the distance between the first sheet material 1B.
In glucose sensor X4 shown in Fig. 9 C, do the cross sectional shape of kapillary 4C circular.More particularly, in glucose sensor X4, on two first and the second sheet material 1C, 2C, form recess 10C, the 20C of semicircle shape, in these recesses 10C, 20C, form first and second 51C of reagent portion, 52C.
Glucose sensor X4 is on drawing, and first and second 51C of reagent portion, 52C form as mutual continuous members, but the 51C of these reagent portions, 52C also can make structure disconnected from each other.In this glucose sensor X4, the opposite distance H is the diameter of the thickness direction of each sheet material 1C, 2C on the kapillary 4C.
In glucose sensor X5 shown in Fig. 9 D, the cross sectional shape of kapillary 4D is done ovalization.More particularly, in glucose sensor X5, on two first that engage one another by dividing plate 3D and the second sheet material 1D, 2D, form recess 10D, the 20D of semicircle shape, on these recesses 10D, 20D, form first and second 51D of reagent portion, 52D.First and second 51D of reagent portion, 52D are by dividing plate 3D and by disconnected from each other.In glucose sensor X5, the opposite distance H is the distance between the position, deep of recess 10D, 20D.
Glucose sensor X6 shown in Figure 10 A and Figure 10 B forms the reagent 70E of portion in the inside of transparent pipe 7E.Glucose sensor X4 shown in glucose sensor X6 and Fig. 9 C similarly, possessing the cross section is the kapillary 71E of toroidal, but is stipulated by pipe 7E on this aspect at kapillary 71E, different with the glucose sensor X4 shown in Fig. 9 C.In this glucose sensor X6, the opposite distance H is the internal diameter of pipe 7E.
Second embodiment
Below, second embodiment of the present invention is described.Wherein, in the present embodiment, when the reference accompanying drawing, for the identical part of member that illustrates in the first embodiment with the front, the mark same-sign.
Figure 11～glucose sensor X7 shown in Figure 14 is as the disposable structure of measuring concentration of glucose by colorimetric, essential structure and the glucose sensor X1 that illustrates previously (Fig. 1～Fig. 3) identical.That is, this glucose sensor X7 has the form that engages first and second sheet material 1,2 by a pair of dividing plate 3F, and by each member 1,2,3F, the kapillary 4F that extends on the length direction of first and second sheet material 1,2 is prescribed down.
In glucose sensor X7, the configuration of the height dimension H ' of kapillary 4F and the 51F of reagent portion and the glucose sensor X1 that illustrates previously (Fig. 1～Fig. 3) different.
Height dimension capillaceous (opposite distance) H ' is below 150 μ m and form.The height dimension H ' of kapillary 4F is preferably set to below the 100 μ m, more preferably below the 75 μ m.But, as whole blood, contain in use under the situation of test portion of blood cell (solid portion), import reliably in order to make the test portion (blood) that carries out to kapillary 4F, the height dimension H ' of kapillary 4F is preferably set to below the 30 μ m.The height dimension H ' of kapillary 4F can adjust by the gauge of dividing plate 3F.
On the other hand, the 51F of reagent portion only is arranged on first sheet material 1.The 51F of this reagent portion forms the solid shape of easy dissolving with respect to blood, for example constitute as containing the member of colour former, electron transport substance and oxidoreducing enzyme.As colour former, electron transport substance and oxidoreducing enzyme, can use the identical article of explanation in the first embodiment.
Shown in Figure 14 A and Figure 14 B, in glucose sensor X7,,, blood is advanced in the inside of kapillary 4F by the capillary force that in kapillary 4F, produces supplying with under the situation of blood to kapillary 4F by opening 40.At this moment, the 51F of reagent portion is built into liquid-phase reaction system 42F by blood dissolves in the inside of kapillary 4F.In liquid-phase reaction system 42F, the colour former color development, its color development degree (coloring degree of liquid-phase reaction system) and the glucose sensor X1 that illustrates previously are (with reference to Fig. 1～Fig. 3) similarly measured.
In glucose sensor X7, also can be clear and definite from the aftermentioned embodiment, by with the opposite distance H ' be set in below the 150 μ m, littler than common, and can shorten minute.Promptly, in glucose sensor X7, for homogenising in liquid-phase reaction system 42F, be included in the 51F of reagent portion target component (colour former, oxidoreducing enzyme, electron transport substance) concentration and the diffusion length of the target component that needs diminishes on short transverse.In addition, even under the situation of consumption of glucose owing to react, the glucose diffusion length of evenly disperseing unreacted glucose to use, also the glucose than common is little on short transverse.Its result in glucose sensor X7, takes place easily for the needed reaction of colour former color development is become, and is used for obtaining shortening as the time of goal response state (liquid-phase reaction system painted), can shorten minute.
Relate to glucose sensor of the present invention, the form that is not limited to illustrate in the present embodiment for example also can be made Figure 15～structure shown in Figure 17.
In glucose sensor X8 shown in Figure 15 A and Figure 15 B, forming the cross section on the first sheet material 1G is the recess 10G of rectangle, forms the reagent 51G of portion in the bottom of this recess 10G.Shown in Figure 15 B, among this glucose sensor X8, the opposite distance H ' be the bottom surface of recess 10G and the distance between the second sheet material 2G.
In glucose sensor X9 shown in Figure 16 A and Figure 16 B, the cross sectional shape of kapillary 4H is become semicircle shape.More particularly, forming the cross section on the first substrate 1H is the recess 10H of semicircle, at the inner face formation reagent 51H of portion of this recess 10H.Shown in Figure 16 B, in this glucose sensor X9, the opposite distance H ' be the degree of depth of recess 10H.
In the glucose sensor X10 shown in Figure 17 A and Figure 17 B, do the cross sectional shape of kapillary 4I circular.More particularly, in glucose sensor X10, on two first and the second sheet material 1I, 2I, form recess 10I, the 20I of semicircle shape, form the reagent 51I of portion at the recess 10I of the first sheet material 1I.Shown in Figure 17 B, in this glucose sensor X10, the opposite distance H ' be the diameter of kapillary 4I.
In glucose sensor X8～X10 of Figure 15～shown in Figure 17, between first and second sheet material, dividing plate is not set, but in the structure of dividing plate was set, the thickness of adding dividing plate was the opposite distance.
In first embodiment and second embodiment, to being illustrated according to injecting light and can measuring the such glucose sensor of constructing of concentration of glucose through light intensity, basis is injected light and catoptrical intensity is measured the glucose sensor that concentration of glucose is constructed like this but the present invention also goes for.Particularly, the glucose sensor that relates to first embodiment of the invention, be not limited to measure the glucose sensor that concentration of glucose constitutes like this, also go for measuring the glucose sensor that concentration of glucose constitutes like this by the electrode method by colorimetric.
Glucose sensor X1～X10 in each embodiment moves test portion by capillary force to constitute, still, also can test portion be moved by the power of pump etc. and constitute, in addition, also may not need to adopt the structure that test portion is moved.
The present invention also goes for the occasion of cholesterol etc. for example of the composition except that glucose in the analyzing blood, in addition, can be applicable to the occasion that test portion beyond the analyzing blood is for example urinated etc.
Embodiment
First embodiment
In the present embodiment, when using under the situation of blood as test portion, give the influence of minute, change by the time of measuring absorbance and inquire into for the height dimension capillaceous in the glucose sensor (opposite distance).
(glucose sensor that uses in the present embodiment)
In the present embodiment, use three kinds of glucose sensors (1)～(3).These glucose sensors (1)～(3) are same structure basically, by the gauge of regulation double sticky tape (dividing plate), and as shown in table 1 such, make height dimension capillaceous (opposite distance) different.
Make as follows each glucose sensor (1)～(3).At first, the interval that a pair of double sticky tape is separated 3mm sticks on first transparent panel of the PET system that is of a size of 10mm * 30mm * 0.2mm.Double sticky tape is stipulated gauge capillaceous, and the thickness of double sticky tape that is used in each glucose sensor (1)～(3) is as shown in table 1.Then, after the reagent liquid that will form shown in the table 1 injects the zone of the 3mm * 3mm between a pair of double sticky tape respectively, dry (30 ℃, 10%Rh) the reagent liquid of air-supply, and form reagent portion.The injection rate IR separately of the reagent liquid when making each glucose sensor (1)～(3), as shown in table 1.That is, the injection rate IR separately of reagent liquid is set according to capacity capillaceous, and glucose sensor (1)～(3) are set like this, that is: when blood was imported to kapillary, the reagent concentration in kapillary reached identical.Then, be bonded on first transparent panel by second transparent panel of double sticky tape with the PET system of 10mm * 30mm * 0.2mm, and the glucose sensor that is used in the present embodiment (1)～(3).
Table 1: the structure of the glucose sensor that uses among first embodiment
In table 1, PQQGDH coughs up the abbreviation of quinoline quinone (PQQ) for the glucose dehydrogenase (GDH) of additional enzyme with arsenic, PMS is the abbreviation of 5-methylphenazinium methylsulfate (5-PMS), MMT is 3-(4,5-Dimethyl-2-thiazolyl)-2, (3-(4 for 5-diphenyl-2H-tetrazolium bromide, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-Thiazolyl blue tetrazolium bromide salt) abbreviation, PIPES is Piperazine-1,4-bis (2-ethanesulfonicacid) (piperazine-1,4-two (2-ethanesulfonic acid)) abbreviation.
The mensuration of absorbance
In the present embodiment, about each glucose sensor (1)～(3), about being the suitable blood of 0mg/dL, 200mg/dL, 400mg/dL or 600mg/dL, change in time absorbance is measured as concentration.
When measuring absorbance,,, at this moment, accept to see through the light of glucose sensor along short transverse irradiates light capillaceous for the zone that reagent portion is set.The irradiation of light is to use light emitting diode to be undertaken by the light of irradiation 630nm.See through light and be subjected to light at photodiode.Absorbance is calculated by following formula.
ABS (absorbance)=log (l
1/ l
2)
In the above-listed formula, l
1For injecting light intensity, l
2For seeing through light intensity.
(measurement result and discussion)
The time dependent measurement result of the absorbance in each glucose sensor (1)～(3) is respectively shown in Figure 18 A～Figure 18 C.
Shown in Figure 18 A, thickness (opposite distance) at double sticky tape (kapillary) is in the glucose sensor (1) of 200 μ m, absorbance changes in time and diminishes, at concentration of glucose is under the situation of 400mg/dL or 600mg/dL, even begin also fully not move closer to for maximum absorbance through 30 seconds from the blood importing.Therefore, in glucose sensor (1), import beginning 30 seconds with the mensuration of interior concentration of glucose difficulty relatively from blood, in addition, if from blood import beginning at 30 seconds with the interior concentration of glucose of measuring accurately, the measurement range of then having to dwindle.
Shown in Figure 18 B, be in the glucose sensor (2) of 100 μ m at the thickness of double sticky tape (kapillary) (opposite distance), even concentration of glucose is 600mg/dL, import beginning about 10 seconds from blood, also fully move closer to for maximum absorbance.Like this, in glucose sensor (2), in concentration of glucose is the scope of 0～600mg/dL, import beginning about 10 seconds at least, can carry out the mensuration of concentration of glucose accurately from blood.
Shown in Figure 18 C, be in the glucose sensor (3) of 60 μ m at the thickness of double sticky tape (kapillary) (opposite distance), even concentration of glucose is 600mg/dL, import beginning about 5 seconds from blood, also fully move closer to for maximum absorbance.Like this, in glucose sensor (3), in concentration of glucose is the scope of 0～600mg/dL, import beginning about 5 seconds at least, can carry out the mensuration of concentration of glucose accurately from blood.
As can be known from these results, under the identical situation of the reagent concentration of liquid-phase reaction system, absorbance is to moving closer to the peaked time, along with the thickness (opposite distance) of double sticky tape (kapillary) diminishes and shortens.Therefore, in glucose sensor, we can say the distance (opposite distance) by the normal direction that shortens the reagent portion in the kapillary, for example this distance preferably below 75 μ m, and can shorten minute below 150 μ m.
Second embodiment
In the present embodiment, using under the situation of glucose solution as test portion, giving the influence of minute, changing by the time of measuring absorbance and inquire into the formation sample attitude of the reagent portion in the glucose sensor.
(glucose sensor that uses among second embodiment)
In the present embodiment, three kinds of glucose sensors (4)～(6) shown in the table 2 have been used.
Glucose sensor (4) forms reagent portion (with reference to Fig. 1～Fig. 3) on two first and second sheet material.In this glucose sensor (4), after on first sheet material, having pasted a pair of double sticky tape, between a pair of double sticky tape, form the first reagent portion, on the other hand, after on second sheet material, having pasted a pair of double sticky tape, between a pair of double sticky tape, form the second reagent portion, form by the first and second reagent portion relative bonding first and second sheet material.In addition, about the structure of glucose sensor (4), about with glucose sensor (1)～(3) different part of first embodiment, be illustrated in the table 2, about table 2 do not have the record structure, be similarly to make with glucose sensor (1)～(3) of first embodiment.
Glucose sensor (5), (6) only form reagent portion on first sheet material, as following formation shown in Figure 2, similarly make with glucose sensor (1)～(3) of first embodiment.
Table 2: the structure of the glucose sensor that uses among second embodiment
(measurement result and discussion)
In the present embodiment, use each glucose sensor (4)～(6), with first embodiment similarly, along with the time changes and has measured absorbance.Absorbance is that the different three kinds of glucose solutions (0mg/dL, 200mg/dL, 400mg/dL) of concentration are measured.The time dependent measurement result of the absorbance in each glucose sensor (4)～(6) is respectively shown in Figure 19 A～Figure 19 C.
Shown in Figure 19 A, in glucose sensor (4),, import beginning about 10 seconds from blood even be under the situation of 600mg/dL at concentration of glucose, fully move closer to for maximum absorbance.Therefore, as glucose sensor (4), in being provided with the glucose sensor (4) of two relative reagent portions, at least in concentration of glucose is the scope of 0～600mg/dL, import beginning about 10 seconds from blood, can carry out the mensuration of concentration of glucose accurately.
Shown in Figure 19 B, in glucose sensor (5), absorbance changes in time and diminishes, and is under the situation of 600mg/dL at concentration of glucose, even begin also not move closer to fully for maximum absorbance through 30 seconds from the blood importing.Therefore, only on single face, be provided with in the glucose sensor (5) of reagent portion, even make the height dimension capillaceous (opposite distance) and the composition of reagent portion identical with glucose sensor (4), also very difficult with the mensuration of interior concentration of glucose from blood importing beginning at 30 seconds, in addition, if from blood import beginning 30 seconds with the interior concentration of glucose of measuring accurately, then measurement range has to diminish.
Shown in Figure 19 C, in glucose sensor (6), can obtain and the same result of glucose sensor (4).
That is, in being provided with the glucose sensor (4) of two relative reagent portions, can obtain in fact with the little situation of opposite distance under (glucose sensor of first embodiment (2), (3)] identical effect.This just means, is forming relatively under the situation of reagent portion, and the first, even, also can shorten minute over there apart under the bigger situation; The second, if set the opposite distance lessly, forming under the situation of reagent portion on a side the sheet material, might be able to not obtain the mensuration of short time.Therefore, in the glucose sensor that two reagent portions are relatively formed, can shorten minute significantly.
Claims (24)
1. an analyzer is characterized in that, comprising:
Be used for making the reaction compartment of the special component of test portion and reagent reaction and be disposed in the described reaction compartment and the reagent portion of when test portion is supplied to described reaction compartment, dissolving, wherein,
Described reagent portion has first relative and second portion mutually on the predetermined surface of the described reaction compartment of regulation.
2. analyzer as claimed in claim 1 is characterized in that:
Described first and second portion by mutually disjunction.
3. analyzer as claimed in claim 1 is characterized in that:
The composition in the described first and the composition of described second portion are different.
4. analyzer as claimed in claim 1 is characterized in that:
Described reagent portion constitutes contains the color development reagent, can carry out the analysis of test portion by colorimetric.
5. analyzer as claimed in claim 1 is characterized in that:
Described predetermined surface comprises the first area that described first is set, and described second portion is set and at the normal direction of the described first area second area relative with described first area;
With the opposite distance setting of described first area and described second area below 300 μ m.
6. analyzer as claimed in claim 5 is characterized in that:
Described opposite distance is more than 30 μ m.
7. analyzer as claimed in claim 5 is characterized in that, comprising:
Have first sheet material of described first area and have described second area and and second sheet material of the described reaction compartment of the described first sheet material joint provisions.
8. analyzer as claimed in claim 7 is characterized in that:
Also comprise engage described first sheet material and described second sheet material and and the dividing plate of the described reaction compartment of these sheet material joint provisions;
Described opposite distance is by described dividing plate regulation.
9. analyzer as claimed in claim 1 is characterized in that:
Described reaction compartment constitutes, and by the capillary force that produces at this reaction compartment test portion is moved.
10. analyzer as claimed in claim 1 is characterized in that:
As described test portion, can use blood.
11. the manufacture method of an analyzer is characterized in that, comprising:
Form operation in the first reagent portion that forms the first reagent portion more than on first substrate;
Form operation in the second reagent portion that forms the second reagent portion more than on second substrate; With
The intermediate that makes the described first and second reagent portion engage one another described first and second substrate relative to each other and form intermediate forms operation.
12. the manufacture method of analyzer as claimed in claim 11 is characterized in that:
Form in the operation in the described first reagent portion, described first substrate is formed with a plurality of first reagent portions;
Form in the operation in the described second reagent portion, described second substrate is formed with a plurality of second reagent portions; And
Also comprise in order at least respectively to contain one described first and the second reagent portion and cut off the cut-out of described intermediate.
13. the manufacture method of analyzer as claimed in claim 11 is characterized in that:
The described first reagent portion and the second reagent portion form as forming mutually different structure.
14. the manufacture method of analyzer as claimed in claim 11 is characterized in that:
The described first reagent portion and the second reagent portion form identical or roughly the same composition.
15. the manufacture method of analyzer as claimed in claim 11 is characterized in that, also comprises:
Before described intermediate forms operation on that carry out and at least one side in described first and second substrate, form described first or the face of the second reagent portion on, keep the operation of dividing plate.
16. an analyzer is characterized in that:
Be to comprise being used for making the special component of test portion and the reaction compartment that reagent reacts, and the analyzer that by the described special component of colorimetric analysis the time, is utilized;
The predetermined surface of stipulating described reaction compartment comprises: be used to keep the reagent retaining zone of reagent and the zone, opposite that relatively has and do not keep reagent in the normal direction and the described reagent retaining zone of described reagent retaining zone;
With the opposite distance setting in described reagent retaining zone and zone, described opposite is below the 150 μ m.
17. analyzer as claimed in claim 16 is characterized in that:
Described opposite distance is below the 100 μ m.
18. analyzer as claimed in claim 17 is characterized in that:
Described opposite distance is below the 75 μ m.
19. analyzer as claimed in claim 16 is characterized in that:
Described opposite distance is more than the 30 μ m.
20. analyzer as claimed in claim 16 is characterized in that:
Described reaction compartment constitutes test portion is moved.
21. analyzer as claimed in claim 20 is characterized in that:
The capillary force that described reaction compartment constitutes by producing at this reaction compartment moves test portion.
22. analyzer as claimed in claim 16 is characterized in that, comprising:
Have first sheet material of described reagent retaining zone and have zone, described opposite and and second sheet material of the described reaction compartment of the described first sheet material joint provisions.
23. analyzer as claimed in claim 22 is characterized in that:
Also comprise engage described first sheet material and described second sheet material and and the dividing plate of the described reaction compartment of these sheet material joint provisions;
Described opposite distance is by described dividing plate regulation.
24. analyzer as claimed in claim 16 is characterized in that:
As described test portion, use the blood that contains blood cell.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003111950A JP2004317308A (en) | 2003-04-16 | 2003-04-16 | Small gap colorimetric analyzing instrument |
| JP111948/2003 | 2003-04-16 | ||
| JP111950/2003 | 2003-04-16 | ||
| JP2003111948A JP2004317307A (en) | 2003-04-16 | 2003-04-16 | Reagent part facing type analyzing instrument and its manufacturing method |
| PCT/JP2004/005434 WO2004092725A1 (en) | 2003-04-16 | 2004-04-15 | Analyzing tool being reduced in distance of diffusion of reagent and method for manufacture thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1774628A true CN1774628A (en) | 2006-05-17 |
| CN1774628B CN1774628B (en) | 2011-04-13 |
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ID=33472366
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200480010320.XA Expired - Fee Related CN1774628B (en) | 2003-04-16 | 2004-04-15 | Analyzing tool being reduced in distance of diffusion of reagent and method for manufacture thereof |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP2004317308A (en) |
| CN (1) | CN1774628B (en) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU642444B2 (en) * | 1989-11-30 | 1993-10-21 | Mochida Pharmaceutical Co., Ltd. | Reaction vessel |
| US5468648A (en) * | 1991-05-29 | 1995-11-21 | Smithkline Diagnostics, Inc. | Interrupted-flow assay device |
| DK0703454T3 (en) * | 1994-09-23 | 2002-04-02 | Unilever Nv | Methods of monitoring and devices for use therewith |
| US5997817A (en) * | 1997-12-05 | 1999-12-07 | Roche Diagnostics Corporation | Electrochemical biosensor test strip |
| US6821410B2 (en) * | 2001-03-07 | 2004-11-23 | Matsushita Electric Industrial Co., Ltd. | Biosensor and method of substrate quantification |
| CN2581995Y (en) * | 2002-09-27 | 2003-10-22 | 上海百傲科技有限公司 | Gene chip colour developing device |
-
2003
- 2003-04-16 JP JP2003111950A patent/JP2004317308A/en active Pending
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2004
- 2004-04-15 CN CN200480010320.XA patent/CN1774628B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004317308A (en) | 2004-11-11 |
| CN1774628B (en) | 2011-04-13 |
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