JPS6122905B2 - - Google Patents
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- Publication number
- JPS6122905B2 JPS6122905B2 JP9890078A JP9890078A JPS6122905B2 JP S6122905 B2 JPS6122905 B2 JP S6122905B2 JP 9890078 A JP9890078 A JP 9890078A JP 9890078 A JP9890078 A JP 9890078A JP S6122905 B2 JPS6122905 B2 JP S6122905B2
- Authority
- JP
- Japan
- Prior art keywords
- layer
- porous
- reagent
- blood
- color
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 210000004369 blood Anatomy 0.000 claims description 59
- 239000008280 blood Substances 0.000 claims description 59
- 239000003153 chemical reaction reagent Substances 0.000 claims description 47
- 239000000463 material Substances 0.000 claims description 39
- 229910052751 metal Inorganic materials 0.000 claims description 33
- 239000002184 metal Substances 0.000 claims description 33
- 238000004458 analytical method Methods 0.000 claims description 29
- 238000011161 development Methods 0.000 claims description 16
- 239000012528 membrane Substances 0.000 claims description 14
- 239000010410 layer Substances 0.000 description 124
- 239000010408 film Substances 0.000 description 39
- 238000000034 method Methods 0.000 description 17
- 238000003892 spreading Methods 0.000 description 16
- 230000007480 spreading Effects 0.000 description 16
- 229910052782 aluminium Inorganic materials 0.000 description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000035699 permeability Effects 0.000 description 6
- 238000004040 coloring Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000011148 porous material Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 238000004445 quantitative analysis Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 238000010030 laminating Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229920000139 polyethylene terephthalate Polymers 0.000 description 3
- 239000005020 polyethylene terephthalate Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N 4-aminoantipyrine Chemical compound CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- -1 polyethylene terephthalate Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- 239000012463 white pigment Substances 0.000 description 2
- PWJNDVAKQLOWRZ-UHFFFAOYSA-N 1-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=CC=C2C(O)=C(S(O)(=O)=O)C=CC2=C1 PWJNDVAKQLOWRZ-UHFFFAOYSA-N 0.000 description 1
- 238000003855 Adhesive Lamination Methods 0.000 description 1
- 229920002799 BoPET Polymers 0.000 description 1
- 229920008347 Cellulose acetate propionate Polymers 0.000 description 1
- 229920001747 Cellulose diacetate Polymers 0.000 description 1
- 229920002284 Cellulose triacetate Polymers 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- NNLVGZFZQQXQNW-ADJNRHBOSA-N [(2r,3r,4s,5r,6s)-4,5-diacetyloxy-3-[(2s,3r,4s,5r,6r)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6s)-4,5,6-triacetyloxy-2-(acetyloxymethyl)oxan-3-yl]oxyoxan-2-yl]methyl acetate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](OC(C)=O)[C@H]1OC(C)=O)O[C@H]1[C@@H]([C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O1)OC(C)=O)COC(=O)C)[C@@H]1[C@@H](COC(C)=O)O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O NNLVGZFZQQXQNW-ADJNRHBOSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000010953 base metal Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000007772 electroless plating Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 229920005787 opaque polymer Polymers 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 238000001579 optical reflectometry Methods 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000001028 reflection method Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229920002050 silicone resin Polymers 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 238000001771 vacuum deposition Methods 0.000 description 1
- 238000007740 vapor deposition Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Description
【発明の詳細な説明】
本発明は多層一体型血液化学分析材料に関する
もので、特に血液中の化学成分を定量するのに全
血、血漿又は血清を用いうることを特徴とするも
のである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a multilayer integrated blood chemistry analysis material, and is particularly characterized in that whole blood, plasma, or serum can be used to quantify chemical components in blood.
血液中の化学成分を分析するために用いる血液
試料としては全血と、面倒な有色・有形成分除去
操作を行なつた後の液体部分、即ち、血漿または
血清とがある。血液の簡易迅速定量又は緊急検査
には、全血を用いることのできる方法が、好都合
なことは言うまでもない。 Blood samples used to analyze chemical components in blood include whole blood and a liquid portion, ie, plasma or serum, after a troublesome procedure for removing colored and formed components. Needless to say, a method that can use whole blood is advantageous for simple and rapid quantitative determination or emergency testing of blood.
技術的困難のために、全血を試料とし、しかも
乾式の簡易迅速な血液化学定量分析法およびその
ための分析材料は、まだ出現していない。血液を
乾式で簡易迅速に定量するものとして、多孔性展
開層を備えたことを特徴とする多層一体型血液化
学分析材料が特開昭49−53888号、同50−137192
号、同51−40191号、同52−3488号、同52−
131786号、同53−24893号、米国特許第3992158
号、同3526480号、同3663374号などの各明細書お
よび第10回国際臨床化学会（Mexico 市、1978
年２月26日〜３月３日）でのJ.N.Eikenberryら
の発表予稿集などに記載されている。これらの血
液化学定量分析材料の基本構成は多孔性展開層と
試薬層との組合わせであるが、試薬層は機能を分
離して、第一試薬層の下に第二試薬層又は発色層
又は検出層又は色素受容層などと呼ばれる複数層
に構成することもある。又、複数試薬層の中間に
色遮蔽層、バリヤ層などと呼ばれる中間層を設け
ることもある。又、展開層中に試薬を包含させて
展開層と試薬層が合体された構造のものもある
が、いずれにしても「展開層」と「試薬層」の二
つの作用層が基本である。 Due to technical difficulties, a simple and rapid dry method for quantitative analysis of blood chemistry using whole blood as a sample and materials for analysis have not yet appeared. A multi-layer integrated blood chemistry analysis material characterized by having a porous development layer is disclosed in JP-A-49-53888 and JP-A-50-137192 for simple and quick dry quantitative determination of blood.
No. 51-40191, No. 52-3488, No. 52-
No. 131786, No. 53-24893, U.S. Patent No. 3992158
No. 3526480, No. 3663374, etc. and the 10th International Society of Clinical Chemistry (Mexico City, 1978).
It is described in the proceedings of the presentation by JNEikenberry et al. The basic composition of these blood chemistry quantitative analysis materials is a combination of a porous development layer and a reagent layer, but the function of the reagent layer is separated, and a second reagent layer or a coloring layer or a coloring layer is placed below the first reagent layer. It may be composed of multiple layers called a detection layer or a dye-receiving layer. Further, an intermediate layer called a color shielding layer, a barrier layer, etc. may be provided between the plurality of reagent layers. There are also structures in which the developing layer and reagent layer are combined by containing a reagent in the developing layer, but in any case, there are basically two active layers: a "developing layer" and a "reagent layer."
この血液化学定量分析材料上に滴下された血液
試料は、多孔性展開層によつて一様に拡げられ試
薬層面に浸入する。試薬層中には、血液中のある
成分と反応して終局的に発色、着色又は変色反応
に導く系が組込まれているので、結局血液中の成
分は比色法によつて定量することができるような
仕組みになつている。 The blood sample dropped onto the blood chemistry quantitative analysis material is uniformly spread by the porous spreading layer and penetrates into the reagent layer surface. The reagent layer contains a system that reacts with certain components in the blood and ultimately leads to color development, coloring, or color change reactions, so the components in the blood cannot be quantified by colorimetry. The system is set up so that it can be done.
かかる既知の多層一体型血液化学定量分析材料
は、試料として血清の他に全血をも適用しうると
前記の文献に記載されているので、記載の方法に
より全血でテストした所、色遮蔽物質が主として
白色顔料からなつているので、色遮蔽性を持たせ
るためには約150μｍ以上の厚さにする必要があ
り、系が濡れている場合はこの厚さでも色遮蔽効
果が充分でないことがわかつた。又系が厚くなる
と製造上の不便の他に血液の浸透性が著るしく阻
害されることがわかつた。そこで種々検討の結
果、既知の多層一体型血液化学分析材料を全血用
として用いられるようにするためには、良好な水
浸透性の色遮蔽層を設けることが不可欠であり、
そのためには多孔性金属膜が非常に有効であるこ
とが判明し、本発明に到達した。 It is stated in the above-mentioned document that such a known multi-layer integrated blood chemistry quantitative analysis material can be applied to whole blood as well as serum as a sample, so when tested with whole blood by the method described, color shielding was observed. Since the material is mainly composed of white pigment, it needs to be approximately 150 μm thick or more in order to have color-shielding properties, and if the system is wet, even this thickness may not provide sufficient color-shielding effect. I understood. It has also been found that when the system becomes thicker, it is not only inconvenient in manufacturing, but also significantly impedes blood permeability. As a result of various studies, we found that in order to use the known multilayer integrated blood chemistry analysis material for whole blood, it is essential to provide a color shielding layer with good water permeability.
It has been found that a porous metal membrane is very effective for this purpose, and the present invention has been achieved.
本発明の目的は全血を試料とし、乾式処理によ
り血液の化学分析を実施できる多層一体型血液化
学定量分析材料を提供することであり、又分析試
薬として有色試薬を含有させることができる多層
一体型血液化学分析材料を提供することである。 An object of the present invention is to provide a multilayer integrated blood chemistry quantitative analysis material that can perform chemical analysis of blood by dry processing using whole blood as a sample. The purpose is to provide body type blood chemistry analysis materials.
本発明は、
(1) 多孔性展開層と試薬層とからなる組合せを含
む多層一体型血液化学分析材料において、多孔
性金属膜からなる水浸透性の色遮蔽層を有する
ことを特徴とする多層一体型血液化学分析材
料、および、
(2) 該多層一体型血液化学分析材料を支持しうる
支持体を有する(1)に記載の多層一体型血液化学
分析材料である。 The present invention provides: (1) A multilayer integrated blood chemistry analysis material comprising a combination of a porous development layer and a reagent layer, which is characterized by having a water-permeable color-shielding layer made of a porous metal film. and (2) the multilayer integrated blood chemistry analysis material according to (1), which has a support capable of supporting the multilayer integrated blood chemistry analysis material.
本発明の多孔性金属膜は、約1000Å以下の薄い
膜であるので、単独にこれをつくることは困難で
ある。一般的には多孔性シートを担体として利用
し、そのシート上に金属膜を形成する方法をと
る。本発明の金属膜は一般概念のピンホールのな
い平膜ではなくて、マクロ的に眺めると膜状に見
えるがミクロ的にはピンホールだらけの膜であつ
て、担体である多孔性シートの孔をふさいだ、即
ち孔をテンテイングした性質のものではなく、担
体の多孔性シートが具備している流体透過性を阻
害することの少ない膜である。多孔性金属膜は流
体透過性と同時に色遮蔽性を有し、この遮蔽効果
は金属の光不透過性に由来するもので、従来の白
色粉体が本質的に光透過性であるのとは対照的に
少量で、すなわち小さい膜厚で充分な光遮蔽効果
があることが特徴である。 Since the porous metal film of the present invention is a thin film of about 1000 Å or less, it is difficult to make it alone. Generally, a method is used in which a porous sheet is used as a carrier and a metal film is formed on the sheet. The metal film of the present invention is not a flat film without pinholes as in the general concept, but it looks like a film from a macroscopic perspective, but microscopically it is a film full of pinholes, and the pores of the porous sheet that is the carrier. It is a membrane that does not block the pores, that is, has tented pores, and does not inhibit the fluid permeability of the porous sheet of the carrier. Porous metal membranes have fluid permeability and color shielding properties, and this shielding effect is derived from the metal's light opacity, unlike conventional white powders which are essentially light transparent. In contrast, it is characterized by a sufficient light shielding effect with a small amount, that is, with a small film thickness.
又前記文献には試薬層中に有色試薬を用いる
時、比色定量の妨害にならないようにその色を隠
蔽する必要があるため、色遮蔽層を有色試薬層の
下に（すなわち、有色試薬層の多孔性展開層から
遠い側の表面に接して）設けることが記載されて
いる。この場合も白色顔料を色遮蔽剤として使用
しているために、約150μｍ以上の層厚でしか
も、水通過性をよくするために層を多孔性にする
特殊な製法が必要である。かかる場合にも本発明
の多孔性金属膜は有用である。即ち厚さ数10μｍ
の多孔性シート状担体の上に多孔性金属膜を形成
したものを別につくつておき、これを第２図中の
６の如く有色試薬層８の下に配置する形式で設け
ることができる。 In addition, in the above document, when a colored reagent is used in the reagent layer, it is necessary to hide the color so as not to interfere with colorimetric determination, so a color shielding layer is placed below the colored reagent layer (i.e., the colored reagent layer is placed under the colored reagent layer). It is described that the material is provided (in contact with the surface of the surface far from the porous spreading layer). In this case as well, since a white pigment is used as a color shielding agent, a special manufacturing method is required to make the layer thicker than about 150 μm and to make the layer porous to improve water permeability. The porous metal membrane of the present invention is also useful in such cases. That is, the thickness is several 10 μm.
A porous metal film formed on a porous sheet-like carrier may be prepared separately and placed under the colored reagent layer 8 as shown in 6 in FIG.
本発明の多層一体型血液化学分析材料の具体例
を模型的に図示して説明する。第１図は単層試薬
型の分析材料の例で、透明支持体１の上に試薬層
２が設けられ、更に上に密着して多孔性金属膜か
らなる色遮蔽層３を有する多孔性展開層４が積層
された形態のものである。ここにおいて透明支持
体１は省くこともでき、試薬層は前述の如く数層
に別けてその機能を分離することができる。多孔
性展開層表面の多孔性金属膜は最上面（すなわ
ち、多孔性展開層の試薬層から遠い側の表面上）
にあつてもよく、又多孔性展開層の両面に多孔性
金属膜が設けられていてもよい。実際の血液化学
分析に際しては矢印Ａ方向から血液試料を滴下
し、液は多孔性展開層を通過しながら一様に拡げ
られ、液は化学組成の変化をうけずに試薬層に到
達、浸透する。試薬層中で特異的な発色反応が行
なわれ、血液中の特定の成分量に比例した発色濃
度が出現するので、矢印Ｂ方向から反射法で比色
定量ができる。さらに多孔性金属膜はその表面が
良好な光反射性であるので本発明の色遮蔽層は比
色定量に際して良好なバツクグラウンドの役割を
はたす。第２図は複数試薬層型の例で、特に試薬
として有色試薬を用いる場合である。透明支持体
１の上に検出層５を設け、その上に、多孔性金属
膜からなる色遮蔽層３を有する多孔性シート状担
体６を重ね、その上に有色試薬層７を設け、更に
その上に多孔性展開層８を設けた形態のものであ
る。なお、いずれの例においても、支持体１を剥
離しうるように構成すれば、不透明又は半透明の
支持体を用いることができる。 A specific example of the multilayer integrated blood chemistry analysis material of the present invention will be explained by schematically illustrating it. Figure 1 shows an example of a single-layer reagent-type analytical material, in which a reagent layer 2 is provided on a transparent support 1, and a porous layer is further provided with a color-shielding layer 3 made of a porous metal film in close contact with the top. The layer 4 has a laminated structure. Here, the transparent support 1 can be omitted, and the reagent layer can be divided into several layers to separate their functions as described above. The porous metal film on the surface of the porous spreading layer is on the top surface (i.e., on the surface of the porous spreading layer farthest from the reagent layer).
Alternatively, porous metal films may be provided on both sides of the porous spreading layer. During actual blood chemistry analysis, a blood sample is dropped from the direction of arrow A, and the liquid is spread uniformly as it passes through the porous development layer, and the liquid reaches and penetrates the reagent layer without undergoing any change in chemical composition. . A specific coloring reaction takes place in the reagent layer, and a coloring density appears that is proportional to the amount of a specific component in the blood, so colorimetric determination can be performed from the direction of arrow B using the reflection method. Furthermore, since the surface of the porous metal film has good light reflectivity, the color shielding layer of the present invention serves as a good background for colorimetric determination. FIG. 2 shows an example of a multi-reagent layer type, especially when a colored reagent is used as the reagent. A detection layer 5 is provided on a transparent support 1, a porous sheet-like carrier 6 having a color shielding layer 3 made of a porous metal film is layered thereon, a colored reagent layer 7 is provided thereon, and a It has a porous spreading layer 8 provided thereon. In any of the examples, an opaque or translucent support can be used as long as the support 1 is configured to be removable.
本発明の色遮蔽層である多孔性金属膜を形成す
る方法は、担体として多孔性シート、例えば、メ
ンブランフイルター、ライスペーパー、紙、和
紙、多孔性粉体膜などの公知の多孔性シート状担
体を予め用意し、その表面に無電解メツキや蒸着
などの方法で金属膜を形成させる方法が一般的で
ある。 The method for forming the porous metal film, which is the color-shielding layer of the present invention, uses a porous sheet as a carrier, for example, a known porous sheet-like carrier such as a membrane filter, rice paper, paper, Japanese paper, or a porous powder film. A common method is to prepare a metal film in advance and form a metal film on its surface using methods such as electroless plating or vapor deposition.
担体になる多孔性シートとして、本発明の血液
化学分析材料の構成要素の一つである多孔性展開
層そのものを利用することは最も好ましい例で、
たとえばメンブランフイルターの如き多孔性展開
層の片面に予め多孔性金属膜を形成しておき、こ
れを試薬層の上にラミネートして接着する方法に
より多層一体化することができる。 The most preferable example is to use the porous spreading layer itself, which is one of the constituent elements of the blood chemistry analysis material of the present invention, as the porous sheet serving as the carrier.
For example, multi-layer integration can be achieved by forming a porous metal film in advance on one side of a porous spreading layer such as a membrane filter, and laminating and adhering this onto the reagent layer.
多孔性金属膜を製造する方法を具体例によつて
説明する。多孔性展開層として有用な膜であるメ
ンブランフイルター（たとえば富士写真フイルム
社製ミクロフイルターFM又はFR300）を多孔性
担体として選び、通常の真空蒸着法によつてアル
ミニウムを真空蒸着してメンブランフイルターの
片面に多孔性金属膜を形成する。メンブランフイ
ルター上に蒸着された金属膜の厚さを実測するこ
とは困難であるので蒸着器中の膜厚モニターに表
示される膜厚を便宜的に採用する。蒸着金属膜の
厚さが約1000Åを超える厚さにすると水または水
溶液の過速度が減少する傾向で、メンブランフ
イルター本来の過特性が変化し、展開層として
の機能も低下する。蒸着金属膜の厚さが約50Å以
下であると色遮蔽効果が低下する。この事実によ
り、蒸着金属膜を色遮蔽層として用いる場合に
は、金属膜の厚さは約50Åから約1000Åまでの範
囲にすることができ、好ましくは約50Åから約
500Åまでの範囲であることが実験により明らか
になつた。かくの如く、多孔性シート担体の上に
多孔性金属膜を形成する方法は、実験的に好適条
件を見出すことができる。金属としては白金、
金、銀、ニツケル、クロム、アルミニウム、亜
鉛、錫、銅などを用いることができるが、白色地
金の金属が好ましい。 A method for manufacturing a porous metal film will be explained using a specific example. A membrane filter (for example, Microfilter FM or FR300 manufactured by Fuji Photo Film Co., Ltd.), which is a membrane useful as a porous development layer, is selected as the porous carrier, and aluminum is vacuum deposited on one side of the membrane filter using an ordinary vacuum deposition method. A porous metal film is formed on the surface. Since it is difficult to actually measure the thickness of the metal film deposited on the membrane filter, the film thickness displayed on the film thickness monitor in the evaporator is used for convenience. When the thickness of the vapor-deposited metal film exceeds about 1000 Å, the overspeed of water or aqueous solution tends to decrease, the inherent overspeed characteristics of the membrane filter change, and the function as a spreading layer also deteriorates. If the thickness of the deposited metal film is less than about 50 Å, the color shielding effect will be reduced. Due to this fact, when a vapor deposited metal film is used as a color blocking layer, the thickness of the metal film can range from about 50 Å to about 1000 Å, preferably from about 50 Å to about
Experiments have revealed that the range is up to 500 Å. As described above, suitable conditions for forming a porous metal film on a porous sheet carrier can be found experimentally. Platinum as a metal,
Gold, silver, nickel, chromium, aluminum, zinc, tin, copper, etc. can be used, but white base metal is preferred.
本発明の多層一体型血液化学分析材料は、多孔
性展開層、試薬層および色遮蔽層を必須の構成要
素（層）として有する血液化学分析材料である
が、必要に応じて、すなわち用途、用いる分析装
置又は分析方法、操作方法又は各層を構成する素
材などにもとづく要請に従つて、支持体、多孔性
展開層から離脱しうる水分蒸発防止カバー、少な
くとも一つの小孔を有する防水性層又は過層の
うちから適宜に選択していずれかをさらに付加し
た構成の多層一体型血液化学分析材料とすること
もできる。 The multilayer integrated blood chemistry analysis material of the present invention is a blood chemistry analysis material that has a porous development layer, a reagent layer, and a color shielding layer as essential components (layers), but it can be used according to needs, i.e., for different purposes. Depending on the requirements of the analytical device or analytical method, the operating method, or the materials constituting each layer, the support, a moisture evaporation prevention cover that can be separated from the porous spreading layer, a waterproof layer with at least one small hole, or a It is also possible to provide a multilayer integrated blood chemistry analysis material having a structure in which any one of the layers is further added by appropriately selecting one of the layers.
支持体を有する場合、支持体は試薬層の多孔性
展開層と反対側の表面に接して設ける。複数の試
薬層を有する場合には試料を滴下する側から最も
遠い試薬層の多孔性展開層と反対側の表面に接し
て透明支持体を設ける。透明支持体はポリエステ
ル（例、ポリエチレンテレフタレート）、ポリカ
ルボネート（例、ビスフエノールＡのポリカルボ
ネート）、セルロースエステル（例、セルロース
ジアセテート、セルローストリアセテート、セル
ロースアセテートプロピオネート、セルロースア
セテートブチレート）等の近紫外線、可視光線、
近赤外線をよく透過しうる（透明性がよい）もの
で、約10μｍから約0.5mmまでの範囲の厚さのフ
イルムを用いることができる。また支持体として
シリコーン樹脂等の離型剤を塗布した半透明又は
不透明な紙、または透明、半透明又は不透明なポ
リマーフイルムのテープを試薬層に貼りつけて設
けることもできる。離型剤を塗布した支持体を用
いる場合、分析するまでは血液化学分析材料の保
護の役目をし、測定する際にはこれを剥してから
測定することができる。 When a support is provided, the support is provided in contact with the surface of the reagent layer opposite to the porous development layer. In the case of having a plurality of reagent layers, a transparent support is provided in contact with the surface of the reagent layer furthest from the side where the sample is dropped, on the side opposite to the porous development layer. The transparent support is made of polyester (e.g., polyethylene terephthalate), polycarbonate (e.g., polycarbonate of bisphenol A), cellulose ester (e.g., cellulose diacetate, cellulose triacetate, cellulose acetate propionate, cellulose acetate butyrate). Near ultraviolet rays, visible light, etc.
A film that can transmit near-infrared rays well (has good transparency) and has a thickness in the range of about 10 μm to about 0.5 mm can be used. Alternatively, a translucent or opaque paper coated with a release agent such as a silicone resin, or a transparent, semitransparent or opaque polymer film tape may be attached to the reagent layer as a support. When using a support coated with a release agent, it serves to protect the blood chemistry analysis material until it is analyzed, and the support can be peeled off before measurement.
多孔性展開層から離脱しうる水分蒸発防止カバ
ーを有する場合、水分蒸発防止カバーは多孔性展
開層を覆うように設ける。水分蒸発防止カバーの
形、素材、設け方は実願昭53−59886号明細書の
記載に従うことができる。 When a moisture evaporation prevention cover that can be separated from the porous development layer is provided, the moisture evaporation prevention cover is provided to cover the porous development layer. The shape, material, and method of providing the moisture evaporation prevention cover can follow the description in the specification of Utility Model Application No. 53-59886.
少なくとも一つの小孔を有する防水性層を有す
る場合、防水性層は多孔性展開層の試薬層から遠
い側の表面に接して設ける。小孔を有する防水性
層における小孔の形、大きさ、その数、防水性層
の形、素材、設け方は実願昭53−59888号明細書
の記載に従うことができる。 When the waterproof layer has at least one small pore, the waterproof layer is provided in contact with the surface of the porous spreading layer on the side far from the reagent layer. The shape, size and number of small holes in the waterproof layer having small holes, the shape, material and method of providing the waterproof layer can be in accordance with the description in the specification of Japanese Utility Model Application No. 53-59888.
血液中の有形成分を除去しうる過層を有する
場合、過層は小孔を有する防水性層の多孔性展
開層に接している表面と反対側の表面に接して設
けられる。血液中の有形成分を除去しうる過層
の形、素材、設け方は実願昭53−77177号明細書
の記載に従うことができる。なお、過層は多孔
性展開層の試薬層から遠い表面に接して設けるこ
ともでき、この場合には過層の上（すなわち
過層の多孔性展開層に接していない表面）を覆う
ようにして水分蒸発防止カバー又は小孔を有する
防水性層を設けることができる。 When having an overlayer capable of removing formed components in blood, the overlayer is provided in contact with the surface of the waterproof layer having small pores opposite to the surface in contact with the porous spreading layer. The shape, material, and method of providing the overlayer capable of removing formed components in the blood can be according to the description in the specification of Japanese Utility Model Application No. 77177/1983. Note that the overlayer can be provided in contact with the surface of the porous development layer that is far from the reagent layer, and in this case, the overlayer should be provided so as to cover the top of the overlayer (i.e., the surface of the overlayer that is not in contact with the porous development layer). A moisture evaporation prevention cover or a waterproof layer with small holes can be provided.
本発明の多層一体型血液化学分析材料を製造す
るには、透明支持体上に塗布方式で試薬層を形成
し、別に製した多孔性金属膜を備えた多孔性展開
層を積層して一体化する方法が一般的である。又
有色試薬を利用する場合には、支持体の上に色検
出層を塗布方式で設け、その上に、別に製した多
孔性金属膜を備えた多孔性シートを設け、更にそ
の上に有色試薬層と多孔性展開層とを塗布又はラ
ミネートによつて設ける。 To manufacture the multilayer integrated blood chemistry analysis material of the present invention, a reagent layer is formed on a transparent support by a coating method, and a porous spreading layer with a separately manufactured porous metal film is laminated and integrated. The most common method is to In addition, when using a colored reagent, a color detection layer is provided on the support by coating, a porous sheet with a separately manufactured porous metal membrane is provided on top of that, and the colored reagent is further applied on top of that. The layer and the porous spreading layer are provided by coating or laminating.
本発明の多層一体型血液化学分析材料は、色遮
蔽層として厚さが1000Å以下の薄い膜厚であるた
めに、全く水分透過性を害することがなく、又素
材として金属を用いているので、色遮蔽性は血液
化学分析材料の乾湿に関係なく完全で、全血の色
又は有色試薬の色を隠蔽する能力にすぐれたもの
である。又製造法も、従来の白色顔料を用いた、
厚膜の特殊製法による多孔性色遮蔽層に較べて、
はるかに容易な方法によることができる。 The multilayer integrated blood chemistry analysis material of the present invention has a thin film thickness of 1000 Å or less as a color shielding layer, so it does not impair water permeability at all, and since metal is used as the material, The color-shielding property is perfect regardless of whether the blood chemistry analysis material is wet or dry, and has an excellent ability to hide the color of whole blood or the color of colored reagents. The manufacturing method also uses conventional white pigments.
Compared to a porous color shielding layer made using a special thick film manufacturing method,
It can be done in a much easier way.
実施例 １
血中グルコース測定用多層一体型の血液化学分
析材料の例。厚さ170μｍの写真材料用親水性下
塗り済みのポリエチレンテレフタレート（PET
と略す。）フイルムの上に、１m2当り次の処方の
試薬層溶液（ゼラチン水溶液）を塗布乾燥して試
薬層とした。Example 1 An example of a multilayer integrated blood chemistry analysis material for measuring blood glucose. 170 μm thick polyethylene terephthalate (PET) with hydrophilic undercoat for photographic materials.
It is abbreviated as ) A reagent layer solution (gelatin aqueous solution) having the following formulation was applied per 1 m 2 of the film and dried to form a reagent layer.
試薬層溶液の組成 10重量％ゼラチン水溶液 210ｇ １−ナフトール−２−スルホン酸 ナトリウム １ｇ ４−アミノアンチピリン 0.52ｇ グルコースオキシダーゼ 13000単位 ペルオキシダーゼ 6700単位 ノニオン界面活性剤 ３ｇ グリセリン 30ｇ NaOHによりPHを6.5に調節する。Composition of reagent layer solution 10% gelatin aqueous solution 210g 1-naphthol-2-sulfonic acid Sodium 1g 4-aminoantipyrine 0.52g Glucose oxidase 13000 units Peroxidase 6700 units Nonionic surfactant 3g Glycerin 30g Adjust PH to 6.5 with NaOH.
次にこの層の上に次の処方の光拡散層分散液を
塗布乾燥し、乾燥後の厚さ15μｍの光拡散層を積
層した。 Next, a light-diffusing layer dispersion having the following formulation was applied and dried on this layer, and a dried light-diffusing layer having a thickness of 15 μm was laminated thereon.
光拡散層分散液の組成
10重量％ゼラチン水溶液 30ｇ
硫酸バリウム 10ｇ
一方、真空蒸着機を用いて、大きさＡ−４サイ
ズ（21cm×29.7cmの長方形）、厚さ150μｍのメン
ブランフイルター（富士フイルムミクロフイルタ
ーFM−300）の出口側表面上に、１×10-6Torr
の真空下で、厚さおよそ200Åのアルミニウム層
を蒸着した。アルミニウムは直径２mmのワイヤー
をタングステンのヘリカルコイル中にセツトし、
およそ1100℃に加熱した。蒸着膜厚は、水晶振動
子膜厚モニターを用いて測定した。かくして製し
たアルミニウム蒸着膜を有するミクロフイルター
を、アルミニウム面を下にして、前記の光拡散層
の上に積層して多孔性展開層とした。積層方法
は、光拡散層が未乾のうちに、そのバインダー物
質であるゼラチンの接着力を利用する方法でラミ
ネートにより接着積層した。Composition of light diffusion layer dispersion: 10% by weight gelatin aqueous solution 30g Barium sulfate 10g Meanwhile, using a vacuum evaporator, a membrane filter of size A-4 (21cm x 29.7cm rectangle) and 150μm thick (Fujifilm Micro) 1×10 -6 Torr on the outlet side surface of the filter FM-300)
An aluminum layer approximately 200 Å thick was deposited under vacuum at . For aluminum, a wire with a diameter of 2 mm is set in a tungsten helical coil.
It was heated to approximately 1100°C. The deposited film thickness was measured using a crystal oscillator film thickness monitor. The thus produced microfilter having the aluminum vapor-deposited film was laminated on the light diffusion layer with the aluminum side facing down to form a porous development layer. As for the lamination method, adhesive lamination was carried out by laminating while the light diffusing layer was still wet, by utilizing the adhesive force of gelatin, which is a binder substance thereof.
上記方法で製した、多孔性金属膜からなる色遮
蔽層を有する多層一体型血液化学分析材料を用い
て、その多孔性展開層上に10μの全血を滴下し
て展延し、PETフイルム側より観察した所全く
血液の赤色は認められなかつた。試薬層中には全
血中のグルコース量に対応した濃度の発色反応が
見られた。 Using the multilayer integrated blood chemistry analysis material having a color shielding layer made of a porous metal film produced by the above method, 10μ of whole blood was dropped onto the porous spreading layer and spread, and the PET film side Upon closer observation, no red color was observed in the blood. A color reaction was observed in the reagent layer at a concentration corresponding to the amount of glucose in whole blood.
実施例 ２
光拡散層を設けなかつたほかは実施例１と同様
に実施して、実施例１と同様な結果を得た。Example 2 The same procedure as in Example 1 was carried out except that the light diffusion layer was not provided, and the same results as in Example 1 were obtained.
第１図および第２図はそれぞれ本発明の多層一
体型血液化学分析材料の具体例を模型的に示す断
面図である。第１図は単一の試薬層を有する血液
化学分析材料を、第２図の複数の試薬層を有する
血液化学分析材料をそれぞれ示す。
１：支持体、２：試薬層、３：多孔性金属膜か
らなる色遮蔽層、４：多孔性展開層、５：検出
層、６：多孔性シート状担体、７：有色試薬層、
８：多孔性展開層、矢印Ａ：血液試料滴下方向、
矢印Ｂ：観察・測定（比色定量）方向。
FIGS. 1 and 2 are cross-sectional views schematically showing specific examples of the multilayer integrated blood chemistry analysis material of the present invention. FIG. 1 shows a blood chemistry analysis material having a single reagent layer, and FIG. 2 shows a blood chemistry analysis material having multiple reagent layers. 1: Support, 2: Reagent layer, 3: Color blocking layer made of porous metal film, 4: Porous development layer, 5: Detection layer, 6: Porous sheet-like carrier, 7: Colored reagent layer,
8: porous spreading layer, arrow A: blood sample dropping direction,
Arrow B: Observation/measurement (colorimetric determination) direction.
Claims (1)
む多層一体型血液化学分析材料において、多孔性
金属膜からなる水浸透性の色遮蔽層を有すること
を特徴とする多層一体型血液化学分析材料。 ２ 該多層一体型血液化学分析材料を支持しうる
支持体を有する特許請求の範囲１に記載の多層一
体型血液化学分析材料。[Scope of Claims] 1. A multilayer integrated blood chemistry analysis material comprising a combination of a porous development layer and a reagent layer, characterized by having a water-permeable color-shielding layer made of a porous metal membrane. All-in-one blood chemistry analysis material. 2. The multilayer integrated blood chemistry analysis material according to claim 1, which has a support capable of supporting the multilayer integrated blood chemistry analysis material.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9890078A JPS5526428A (en) | 1978-08-14 | 1978-08-14 | Multi-layer incorporating type blood chemical analysis material |
| US06/066,363 US4255384A (en) | 1978-08-14 | 1979-08-14 | Multilayered integral element for the chemical analysis of the blood |
| DE19792932973 DE2932973A1 (en) | 1978-08-14 | 1979-08-14 | INTEGRAL MULTILAYERED MATERIAL FOR CHEMICAL ANALYSIS OF BLOOD |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9890078A JPS5526428A (en) | 1978-08-14 | 1978-08-14 | Multi-layer incorporating type blood chemical analysis material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5526428A JPS5526428A (en) | 1980-02-25 |
| JPS6122905B2 true JPS6122905B2 (en) | 1986-06-03 |
Family
ID=14231995
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9890078A Granted JPS5526428A (en) | 1978-08-14 | 1978-08-14 | Multi-layer incorporating type blood chemical analysis material |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5526428A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11471939B2 (en) | 2002-12-09 | 2022-10-18 | University Of Washington | Methods of nanostructure formation and shape selection |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109580938A (en) * | 2019-01-11 | 2019-04-05 | 广州万孚生物技术股份有限公司 | Loading bottom plate and immuno-chromatography detection device containing the loading bottom plate |
-
1978
- 1978-08-14 JP JP9890078A patent/JPS5526428A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11471939B2 (en) | 2002-12-09 | 2022-10-18 | University Of Washington | Methods of nanostructure formation and shape selection |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5526428A (en) | 1980-02-25 |
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