JP4352109B2 - Biosensor - Google Patents

Description

表１の（ａ）および（ｂ）に示すように湾曲部６に付着することによる、全血のロスは極微量であり、全血が半球状にならず広がってしまうことによる、サンプル採取の失敗はない。表１の（ｃ）に示すサンプル量０．６μＬまたは０．９μＬの時、すなわち３個のサンプル滴が各々０．２μＬまたは０．３μＬの時には、サンプルがサンプル保持部２に移動し終わる前に、次のサンプルが試料吸引孔１まで到着すれば採取ができたが、それ以外の場合は、気泡がサンプル保持部２に入るために、うまくサンプルを採取できなかった。以上の結果は、皮膚上の極微量なサンプルの採取が、目の悪い人にとっても良好に採取されることを示す。
【００３３】
次に、皮膚上の液体を採取する場合を代表例として、更に図面を参照しつつ説明する。図２はバイオセンサをその操作工程順に示す平面図である。このバイオセンサの構成としては、サンプル保持部２をもつ電極構成部１１と自身が移動することでサンプルをかき集めるサンプル採取機構部１２から構成される。サンプルをかき集めるサンプル採取機構部１２は、移動した際にサンプルをかき集めるサンプル貯留部１３と電極構成部１１の両サイドを挟みながら移動する副骨格１４から構成される。さらにサンプル貯留部１３内部は開けた空間になっており、サンプル採取機構部１２がサンプルをかき集めながら移動する際、サンプルはすべてこのサンプル貯留部１３内に貯留される。実施例１と同様にサンプルを配置する広い面積部３とサンプル保持部２を持ち、サンプル保持部２には定量測定を行うための試薬反応層及びサンプルをサンプル保持部２に導き入れるための界面活性剤層が分注してある。サンプルは下記に記載する操作によって、面積部３からサンプル貯留部１３、試料吸引孔１、サンプル保持部２へと移動する。このバイオセンサはサンプルを採取する時には、装置に接続された状態で使用されるので、このバイオセンサを直接持つ必要はなく、装置をもってサンプルを採取するための動作を行う。
【００３４】
これより、サンプル採取方法を記載する。まず、装置に接続されたバイオセンサの先端に、バイオセンサの先端部とサンプル採取機構部１２のサンプル貯留部１３と副骨格１４によって囲まれた広い面積部３内に、皮膚上に静置されているサンプル５があるように装置を移動させる。
【００３５】
次にサンプル貯留部１３の面積部３に面した湾曲部１５を皮膚と密着させながら、サンプル採取機構部１２を矢印１６の方向に移動させると、サンプル５はサンプル貯留部１３にかき取られてサンプル貯留部１３に貯留される。図１２の（ｃ）はサンプル採取機構部１２が移動し、面積部３の面積が０付近の状態である。サンプルは図１２の（ｃ）の（ｃ）中１８で示される位置にある。さらにサンプル採取機構部１２を矢印１６の方向に移動させると、図１２の（ｄ）に示すようにサンプル貯留部１３内の空間にバイオセンサの電極構成部１１の先端が入り込むことにより、サンプル貯留部１３が狭められて、行き場を失ったサンプル１８はサンプル保持部２内の界面活性剤の作用により、サンプル保持部２へと移動する。
【００３６】
この際、皮膚と密着させる湾曲部１５の材料を、弾力性のある、例えばゴム製などにするか、もしくは湾曲部１５の皮膚と接触させる部分にワイパーを弾力性のある、例えばゴム製などにより作製することで、皮膚と密着させながら移動させることによる痛みを、全くなくしてしまうことが可能であり、かつ湾曲部１５と皮膚との間の隙間にサンプルが入り込むことを確実に防ぐことができる。
【００３７】
このバイオセンサで、サンプル保持部２の形状を幅０．８ｍｍ 高さ１５０μｍ 奥行き３ｍｍ（容量 約０．３６μＬ）のものを作製した。このサンプル保持部２に試薬反応層として０．５％ヒドロキシエチルセルロース、１％フェリシアン化カリウム、５００ＩＵ／ｍｌ水溶液を１μＬ分注し、５０℃１０分間乾燥した。また、界面活性剤層として１．０％トリトンＸ−４０５水溶液を０．６μＬ分注し、４０℃５分間乾燥した。サンプルを配置する面積部３の径ｒ２は６ｍｍとし、長さｈ２は２４ｍｍとした。皮膚上に０．４μＬ、０．６μＬ、０．９μＬ、１．２μＬ、１．５μＬの全血を静かに滴下し、半球状の全血採取の実験を１０回行った。サンプル保持部２一杯に全血が採取されたか否かを目視観察することにより評価した。また、実験者は乱視を持ち視力が０．０３であり、また全血を配置した皮膚と目の距離は約６０ｃｍとした。結果を表２の（ａ）に示す。なお、全血を９回以上採取できた場合を○、５〜８回採取できた場合を△、４回以下しか採取できなかった場合を×で示す。
【００３８】
さらに、全血を半球状から皮膚上に広げた状態に配置したもので、上記と同様の実験を行った。結果を表２の（ｂ）に示す。なお、全血を９回以上採取できた場合を○、５〜８回採取できた場合を△、４回以下しか採取できなかった場合を×で示す。
【００３９】
さらに、図２の（ｂ）中１７ａ、１７ｂ、１７ｃの３カ所に全血を３等分して配置し、上記と同様の実験を行った。結果を表２の（ｃ）に示す。なお、全血を９回以上採取できた場合を○、５〜８回採取できた場合を△、４回以下しか採取できなかった場合を×で示す。
【００４０】
【表２】

表２に示すようにサンプルの状態による、すなわち半球状になっていても、広がっていても、分裂していても、これらによる差はない。以上の結果は、皮膚上の極微量なサンプルの採取が、目の悪い人にとっても良好に採取されることを示す。
【００４１】
次に、皮膚上の液体を採取する場合を代表例として、更に図面を参照しつつ説明する。図３はバイオセンサをその操作工程順に示す平面図である。このバイオセンサの構成としては、サンプル保持部２をもつ電極構成部１１と自身が移動することでサンプルをかき集めるサンプル採取ワイヤー２１とこのサンプル採取ワイヤー２１の初期位置を決定づける固定部２２から構成される。このサンプル採取ワイヤー２１は電極構成部１１の両サイドを挟みながら移動することができ、その先端部は固定部２２の内側にある。このバイオセンサは実施例２と同様にサンプルを配置する広い面積部３とサンプル保持部２を持ち、サンプル保持部２には定量測定を行うための試薬反応層及びサンプルをサンプル保持部２に導き入れるための界面活性剤層が分注してある。サンプルは下記に記載する操作によって、面積部３から試料吸引孔１、サンプル保持部２へと移動する。このバイオセンサはサンプルを採取する時には、装置に接続された状態で使用されるので、このバイオセンサを直接持つ必要はなく、装置をもってサンプルを採取するための動作を行う。
【００４２】
これより、サンプル採取方法を記載する。まず、装置に接続されたバイオセンサの先端の、電極構成部１１の先端部とサンプル採取ワイヤー２１によって囲まれた広い面積部３内に、皮膚上に静置されているサンプル５があるように装置を移動させる。
【００４３】
次にサンプル採取ワイヤー２１を、固定部２２を皮膚と密着させながら、矢印２３の方向に移動させると、サンプル５はサンプル採取ワイヤー２１にかき取られながら進む。図３の（ｂ）はサンプル採取ワイヤー２１の移動が終了した瞬間の状態を示している。行き場を失ったサンプルはサンプル保持部２内の界面活性剤の作用により、サンプル保持部２へと移動する。
【００４４】
この際、皮膚と密着させるサンプル採取ワイヤー２１の材料は、移動をスムーズに行うために、弾力性のある、例えばゴム製などや撥水化処理を施してある厚さ２００μｍ以下のポリエチレンテレフタレートなどが好ましいが、弾力性があるものであれば限定されるものではない。さらにサンプル採取ワイヤー２１の皮膚と接触させる部分にワイパーを弾力性のある、例えばゴム製などにより作製することで、皮膚と密着させながら移動させることによる痛みを、全くなくしてしまうことが可能であり、かつサンプル採取ワイヤー２１と皮膚との間の隙間にサンプルが入り込むことを確実に防ぐことができる。
【００４５】
このバイオセンサで、サンプル保持部２の形状を幅０．８ｍｍ 高さ１５０μｍ 奥行き３ｍｍ（容量 約０．３６μＬ）のものを作製した。このサンプル保持部２に試薬反応層として０．５％ヒドロキシエチルセルロース、１％フェリシアン化カリウム、５００ＩＵ／ｍｌ水溶液を１μＬ分注し、５０℃１０分間乾燥した。また、界面活性剤層として１．０％トリトンＸ−４０５水溶液を０．６μＬ分注し、４０℃５分間乾燥した。サンプルを配置する面積部３の径ｒ３は８ｍｍとし、角度ｄ３は２７０度とした。皮膚上に０．４μＬ、０．６μＬ、０．９μＬ、１．２μＬ、１．５μＬの全血を静かに滴下し、半球状の全血採取の実験を１０回行った。サンプル保持部２一杯に全血が採取されたか否かを目視観察することにより評価した。また、実験者は乱視を持ち視力が０．０３であり、また全血を配置した皮膚と目の距離は約６０ｃｍとした。結果を表３の（ａ）に示す。なお、全血を９回以上採取できた場合を○、５〜８回採取できた場合を△、４回以下しか採取できなかった場合を×で示す。
【００４６】
さらに、全血を半球状から皮膚上に広げた状態に配置したもので、上記と同様の実験を行った。結果を表３の（ｂ）に示す。なお、全血を９回以上採取できた場合を〇、５〜８回採取できた場合を△、４回以下しか採取できなかった場合を×で示す。
【００４７】
さらに、図３の（ｂ）中２４ａ、２４ｂ、２４ｃの３カ所に全血を３等分して配置し、上記と同様の実験を行った。結果を表３の（ｃ）に示す。なお、全血を９回以上採取できた場合を○、５〜８回採取できた場合を△、４回以下しか採取できなかった場合を×で示す。
【００４８】
【表３】

表３に示すようにサンプルの状態による、すなわち半球状になっていても、広がっていても、分裂していても、これらによる差はない。以上の結果は、皮膚上の極微量なサンプルの採取が、目の悪い人にとっても良好に採取されることを示す。
【００４９】
比較例として、皮膚上の液体を採取する場合を代表例として、更に図面を参照しつつ説明する。図４の（ｅ）はバイオセンサの斜視図ある。このバイオセンサは、試料吸引孔１を直接サンプルに接触させることで、サンプルをサンプル保持部２にサンプルを移動させる。このバイオセンサはサンプルを採取する時には、装置に接続された状態で使用されるので、このバイオセンサを直接持つ必要はなく、装置をもってサンプルを採取するための動作を行う。
【００５０】
このバイオセンサで、サンプル保持部２の形状を幅０．８ｍｍ 高さ１５０μｍ 奥行き３ｍｍ（容量 約０．３６μＬ）のものを作製した。このサンプル保持部２に試薬反応層として０．５％ヒドロキシエチルセルロース、１％フェリシアン化カリウム、５００ＩＵ／ｍｌ水溶液を１μＬ分注し、５０℃１０分間乾燥した。また、界面活性剤層として１．０％トリトンＸ−４０５水溶液を０．６μＬ分注し、４０℃５分間乾燥した。皮膚上に０．４μＬ、０．６μＬ、０．９μＬ、１．２μＬ、１．５μＬの全血を静かに滴下し、半球状の全血採取の実験を１０回行った。サンプル保持部２一杯に全血が採取されたか否かを目視観察することにより評価した。また、実験者は乱視を持ち視力が０．０３であり、また全血を配置した皮膚と目の距離は約６０ｃｍとした。結果を表４の（ａ）に示す。なお、全血を９回以上採取できた場合を○、５〜８回採取できた場合を△、４回以下しか採取できなかった場合を×で示す。
【００５１】
さらに、全血を半球状から皮膚上に広げた状態に配置したもので、上記と同様の実験を行った。結果を表４の（ｂ）に示す。なお、全血を９回以上採取できた場合を○、５〜８回採取できた場合を△、４回以下しか採取できなかった場合を×で示す。
【００５２】
さらに、３カ所に全血を３等分して配置し、上記と同様の実験を行った。結果を表４の（ｃ）に示す。なお、全血を９回以上採取できた場合を○、５〜８回採取できた場合を△、４回以下しか採取できなかった場合を×で示す。
【００５３】
【表４】

上記実験の結果で失敗の原因は、表４の（ａ）においては、試料吸引孔１以外の部分に全血を接触させてしまい、全血を潰してしまったり、バイオセンサの裏側に付けてしまったりしたのがほとんどである。表４の（ｂ）においては、前記原因に加えて、うまく接触させたにも関わらず、気泡が入ってしまうことによるものである。表４の（ｃ）の場合、このバイオセンサにおいては、分裂した血液滴の１個しか使用できないので、表４の（ａ）の失敗原因と一致する。以上の結果は、サンプルが極微量になると幅０．８ｍｍ、高さ１５０μｍの試料吸引孔１を接触させることが目の悪い人にとっては非常に難しいということを示している。
【発明の効果】
【００５４】
このように本発明によれば、極微量のサンプルであっても、またたとえサンプルが半球状でなく潰れて広がっていても、またたとえサンプルが複数に分裂していても、それらの全てを簡便な操作だけでかき集めることができ、目的の位置まで運び、利用することができる。
【図面の簡単な説明】
【図１】本発明の一実施の形態によるバイオセンサをその操作工程順に示す平面図である。
【図２】本発明の別の実施の形態によるバイオセンサをその操作工程順に示す平面図である。
【図３】本発明の別の実施の形態によるバイオセンサをその操作工程順に示す平面図である。
【図４】従来技術の形態によるバイオセンサをその作製工程順に示す平面図である。
【符号の説明】
１ 試料吸引孔
２ サンプル保持部
３ 面積部
４ 測定装置端部
５ サンプル
６ 湾曲部
７ 移動方向
８ａ サンプル配置位置
８ｂ サンプル配置位置
８ｃ サンプル配置位置
１１ 電極構成部
１２ 採取機構部
１３ サンプル貯留部
１４ 副骨格
１５ 湾曲部
１６ 移動方向
１７ａ サンプル配置位置
１７ｂ サンプル配置位置
１７ｃ サンプル配置位置
１８ サンプル
２１ サンプル採取ワイヤー
２２ 固定部
２３ 移動方向
２４ａ サンプル配置位置
２４ｂ サンプル配置位置
２４ｃ サンプル配置位置
ｒ１ 実施例１で用いたバイオセンサ内の寸法
ｈ１ 実施例１で用いたバイオセンサ内の寸法
ｒ２ 実施例２で用いたバイオセンサ内の寸法
ｈ２ 実施例２で用いたバイオセンサ内の寸法
ｒ３ 実施例３で用いたバイオセンサ内の寸法
ｄ３ 実施例３で用いたバイオセンサ内の角度
３１ 基板
３２ リード部
３３ リード部
３４ 測定電極
３５ 対電極
３６ 界面活性剤層
３８ カバー
４０ 上カバー
４１ 金属膜
４２ スリット[0001]
  The present invention relates to various trace amounts or extremely small amounts of living bodies.LiquidCollect samples easily or reliably for food samples such as fruit juicebe able toIt relates to a biosensor.
[0002]
BACKGROUND OF THE INVENTION
Conventionally, various devices have been proposed that can easily quantify specific components in biological fluids and foods without diluting or stirring the sample. In particular, a perspective view of a biosensor with a small amount of sample is shown in FIG. Further, FIGS. 4A to 4E show the biosensors in the order of manufacturing steps, and a method for manufacturing the biosensors will be described below with reference to the drawings. 31 is an insulating substrate made of polyethylene terephthalate, and 41 is a metal film formed on the entire surface. The metal film 41 is divided into two regions by forming a concave slit 42 in the metal film 41 on the substrate 31 by half cutting with a blade. Two covers 38 are provided so as to cross the divided metal film 41, and the measurement electrode 34 and the counter electrode 35 to which the sample is applied, and the lead portions 32 and 33 for applying a voltage to both the electrodes. Is forming. Further, a reagent reaction layer is formed on the measurement electrode 34 and the counter electrode 35, and a surfactant layer 36 is formed on the reagent reaction layer. Furthermore, the necessary amount of sample is determined by providing the upper cover 40 and limiting the volume of the sample holding part 2 on the measurement electrode 34 and the counter electrode 35. This biosensor quantifies the substrate concentration in the sample as follows. First, prepare a sample. At this time, the required amount of sample is about 3.0 μL. When the sample supply hole 1 having a width of 2.0 mm and a height of 250 μm is brought into contact with the sample, the sample moves on the surfactant layer 36 by the action of the surfactant layer 36 formed on the reagent reaction layer. To do. In this way, the sample is filled and supplied to the sample holder 2 having a width of 2.0 mm, a height of 250 μm, and a length of 6 mm of the biosensor. As a result, the reagent reaction layer is dissolved, and an enzyme reaction proceeds between the substrate in the sample and the oxidoreductase of the reagent reaction layer. Along with this enzyme reaction, the electron acceptor is reduced. After a certain time, a voltage is applied to the sensor electrode to electrochemically oxidize the reduced electron acceptor, and the substrate concentration in the sample can be determined from the oxidation current value obtained at this time.
[0003]
The amount of sample required for the biosensor produced by the above technique is about 3 μL. However, this biosensor cannot measure accurately if the sample amount is insufficient, and the sensor must be discarded. Therefore, it is actually necessary to prepare a sample of 5 μL or more for one measurement.
[0004]
Food-related samples such as fruit juice are not as much as 5 μL. If it is at least several times this amount, preparations can be made without problems. However, since biological fluids, particularly blood and interstitial fluids, are punctured by using a puncture device such as a lancet and discharged, this is a painful operation. Since this pain increases as the sample amount increases, the sample amount is preferably as small as possible.
[Problems to be solved by the invention]
[0005]
In order to reduce the amount of sample, the shape of the sample holding part was produced with a width of 0.8 mm, a height of 150 μm, and a depth of 3.0 mm, and the required sample amount was reduced to 0.5 μL or less.
[0006]
When the sample volume is 5 μL, the size of the sample droplet is about 2.5 mm in diameter and 1.2 mm in height in a hemispherical state. It is not difficult to bring a sample supply hole having a width of 2.0 mm and a height of 250 μm into contact with a sample of this size, even for a person with a visual acuity of about 0.05.
[0007]
However, when the sample volume becomes 0.5 μL, the size of the sample droplet becomes hemispherical, with a diameter of about 1.2 mm and a height of about 0.6 mm. It is very difficult to contact the drop.
[0008]
In particular, this biosensor is mostly used by diabetic patients for daily blood glucose measurement, and many people have diminished vision because of diabetes. It is not acceptable at all.
[0009]
In other words, in the case of biosensors that aim to measure biological fluids that cause pain when the sample is drained, for example, a substance to be detected in blood, the sample is retained to reduce pain when the sample is drained. Even if the volume of the part is reduced to reduce the required sample amount, there is a problem that the sample supply is very difficult.
[0010]
As another problem, when a 5 μL sample is prepared using the biosensor produced by the above-described conventional technology, the sample does not form a spherical shape but is crushed and spread. When the reservoir height is 200 μm or less and the sample supply hole with a height of 250 μm is brought into contact, the sample does not move well, the sample amount is insufficient, or bubbles are involved and the sample is moved to the sample holder. The phenomenon that hinders accurate measurement is likely to occur.
[0011]
For example, when such a problem occurs in a diabetic patient, the measurement must be performed again, and an economic and painful burden is generated on the patient himself.
[0012]
Another problem is that, when preparing a sample, if the sample droplet fails and breaks into multiple droplets, small ones are difficult to see and are not used as a cause of sample shortage. The sample will be discarded.
[0013]
For example, when such a problem occurs in a diabetic patient, it is necessary to drain the blood again in some cases, and a painful burden is generated on the patient himself.
[0014]
An object of the present invention is to provide a sample collection method and a sample collection tool that make it possible to easily collect a sample such as a body fluid present in a very small amount on the surface of a living body typified by skin.
[0015]
Another object of the present invention is to provide a sample collection method and a sample collection tool that can efficiently use a collected sample.
[0016]
It is still another object of the present invention to provide a sample collection method and a sample collection tool that can reliably collect all samples regardless of the state in which the samples to be collected exist or are distributed. .
[0017]
Furthermore, another object of the present invention is to provide a quantitative device that enables quantitative measurement with only a very small amount of sample by combining a sample collection unit with a quantitative device.
[0018]
[Means for Solving the Problems]
  The present inventionThe baySong partSkeleton withAnd a connector portion that is connected to the inside of the quantitative device and extends from the curved portion;,in frontThe curved part includes the sample suction hole and the reagent reaction layer.HaveSample retentionPartPreparationA biosensor having an area surrounded by the skeleton, wherein the curved portion includes a sample holding portion having a sample suction hole and a reagent reaction layer, and the biosensor is configured to collect a sample. In this case, the sample on the sample arrangement surface is in the area portion, and the curved portion is moved so that the sample is collected in one place, and the collected sample is transferred to the sample through the sample suction hole. Introduced and held in the sample holder,It relates to a biosensor. By making the portion to be collected in a curved structure in this way, the collected sample can be collected more effectively in one place.
[0019]
  The biosensor of the present invention isIn the skeleton,The curved portion andAboveIt is possible to attach an elastic wiper to eliminate the gap with the sample placement surface. By attaching the wiper in this manner, the wiper can collect the sample more effectively when moving on the sample placement surface.
[0020]
  In another aspect of the present invention, an electrode component having a sample holding portion on which a reagent reaction layer is formed and a sample are collected in one place, and all or a part of the electrode component is relatively moved. A possible sample collection mechanism, and the sample collection mechanismDepartment and frontBetween the electrode componentsThe above sandwiched between bothClosedA space is formed,And the sump in the closed spaceWhen the sample collection mechanism moves toward the electrode component,A biosensor is provided that is introduced into the sample holder.
[0021]
  In the biosensor of the present invention, when the collection mechanism is moved, while collecting the sample,It becomes possible to collect the collected samples in one place more effectively.
[0022]
  The sample collection mechanism section has a sample storage section for storing the collected sample, for example.The sample existing in the closed space is stored in the sample storage unit when the sample collection mechanism unit moves toward the electrode configuration unit, and the sample stored in the sample storage unit is stored in the sample storage unit. The collection mechanism moves and the tip of the electrode component enters the sample reservoir, and is introduced into the sample holder.The sample holding part may have a sample suction hole. In this case, it is preferable that the electrode configuration portion moves the sample collection mechanism portion toward the electrode configuration portion so that the sample suction hole enters the sample collection mechanism portion.
[0023]
  The sample collection mechanism unit is movable relative to the electrode configuration unit, and a sample collection wire for introducing the sample collected to the sample holding unit, a fixing unit for determining an initial position of the sample collection wire, May have.
[0024]
  With such a biosensor, all samples are collected by a simple operation regardless of the amount of the sample, whether it is in the state of the sample, for example, spread in a planar shape or divided into a plurality of droplets. It becomes possible to do.Moreover, theseBiosensorSince it has a very simple structure, it can be applied to a quantification apparatus using a biosensor as a detection means, so that even a very small sample of 1.0 μL or less can be sampled by a simple operation. And sample supply becomes possible.
[0025]
DETAILED DESCRIPTION OF THE INVENTION
  Hereinafter, the present invention will be described with reference to the drawings, taking a case of collecting a liquid on the skin as a representative example. FIG. 1 is a plan view showing biosensors in the order of their operation steps. The biosensor has a wide area portion 3 and a sample holding portion 2 surrounded by a shape in which a semicircular shape and a rectangular shape in which a sample is arranged are combined, and the sample holding portion 2 is used for quantitative measurement. A reagent reaction layer and a surfactant layer for introducing the sample into the sample holding unit 2 are dispensed. The sample moves from the area portion 3 to the sample suction hole 1 and the sample holding portion 2 by the operation described below. The broken line 4 shown in FIG. 1 in this biosensor(Measurement device end)Two rectangular portions on the left side are connector portions of the biosensor, and are connected to the inside of the apparatus when collecting a sample. Therefore, when collecting a sample, it is not necessary to have this biosensor directly, and an operation for collecting the sample is performed by the apparatus.
[0026]
  From this, a sample collection method will be described. First, the biosensor connected to the deviceCurvedThe apparatus is moved so that the sample 5 is placed on the skin within the wide area 3 surrounded by the shape of the semicircle and the rectangle combined by the part 6 and the apparatus.
[0027]
  Next, facing the semicircular area 3CurvedWhen the device is moved in the direction of the arrow 7 while the part 6 is in close contact with the skin, the sample 5 isCurvedIt contacts the part 6, further moves to the sample suction hole 1, and further moves into the sample holding part 2 by the action of the surfactant in the sample holding part 2.
[0028]
  At this time, close contact with the skinCurved part6 material is made elastic, such as rubber, orCurved partIt is possible to eliminate the pain caused by moving the wiper while being in close contact with the skin by making the wiper elastic, for example, made of rubber or the like, at the portion to be brought into contact with the skin of 6 andCurved partIt is possible to reliably prevent the sample from entering the gap between 6 and the skin.
[0029]
With this biosensor, a sample holding portion 2 having a width of 0.8 mm, a height of 150 μm, and a depth of 3 mm (capacity of about 0.36 μL) was produced. 1 μL of 0.5% hydroxyethyl cellulose, 1% potassium ferricyanide, and 500 IU / ml aqueous solution was dispensed as a reagent reaction layer to the sample holder 2 and dried at 50 ° C. for 10 minutes. Further, 0.6 μL of 1.0% Triton X-405 aqueous solution was dispensed as a surfactant layer and dried at 40 ° C. for 5 minutes. The diameter r1 described in the area portion 3 in the shape of the semicircular shape and the rectangular shape in which the sample is arranged was 6 mm, and h1 was 6 mm. 0.4 μL, 0.6 μL, 0.9 μL, 1.2 μL, and 1.5 μL of whole blood was gently dropped on the skin, and hemispherical whole blood collection experiments were performed 10 times. It was evaluated by visually observing whether or not whole blood was collected in one sample holder 2. The experimenter had astigmatism and a visual acuity of 0.03, and the distance between the skin where the whole blood was placed and the eyes was about 60 cm. The results are shown in Table 1 (a). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0030]
Furthermore, the same experiment as described above was performed with the whole blood arranged in a hemispherical shape spread on the skin. The results are shown in Table 1 (b). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0031]
Further, the whole blood was divided into three equal parts at three positions 8a, 8b, and 8c in FIG. 1B, and the same experiment as described above was performed. The results are shown in Table 1 (c). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0032]
[Table 1]

  As shown in Table 1 (a) and (b)Curved partThe loss of whole blood due to adhering to 6 is extremely small, and there is no failure in sample collection due to the whole blood spreading without becoming hemispherical. When the sample amount shown in (c) of Table 1 is 0.6 μL or 0.9 μL, that is, when three sample droplets are 0.2 μL or 0.3 μL, respectively, before the sample finishes moving to the sample holder 2 When the next sample arrived at the sample suction hole 1, the sample could be collected, but in other cases, the sample could not be collected well because the bubbles entered the sample holding unit 2. The above results indicate that collection of a very small amount of sample on the skin is well collected even for a person with bad eyes.
[0033]
Next, a case where the liquid on the skin is collected will be described as a representative example with reference to the drawings. FIG. 2 is a plan view showing the biosensor in the order of its operation steps. As a configuration of this biosensor, an electrode configuration unit 11 having a sample holding unit 2 and a sample collection mechanism unit 12 that collects a sample by moving itself are configured. The sample collection mechanism unit 12 that collects samples includes a sample storage unit 13 that collects samples when moved and a sub-skeleton 14 that moves while sandwiching both sides of the electrode configuration unit 11. Further, the inside of the sample storage unit 13 is an open space, and when the sample collection mechanism unit 12 moves while collecting the sample, all the samples are stored in the sample storage unit 13. Similar to the first embodiment, the sample holding section 2 has a large area 3 for arranging the sample and the sample holding section 2. The sample holding section 2 has a reagent reaction layer for performing quantitative measurement and an interface for introducing the sample into the sample holding section 2. The activator layer is dispensed. The sample moves from the area portion 3 to the sample storage portion 13, the sample suction hole 1, and the sample holding portion 2 by the operation described below. Since this biosensor is used in a state of being connected to an apparatus when a sample is collected, it is not necessary to directly have this biosensor, and an operation for collecting a sample is performed by the apparatus.
[0034]
From this, a sample collection method will be described. First, the biosensor connected to the device is placed on the skin in the wide area 3 surrounded by the biosensor tip, the sample reservoir 13 and the sub-skeleton 14 of the sample collection mechanism 12. The device is moved so that there is a sample 5 that is present.
[0035]
  Next, the area 3 of the sample reservoir 13 was faced.Curved partWhen the sample collection mechanism 12 is moved in the direction of the arrow 16 while keeping 15 in close contact with the skin, the sample 5 is scraped by the sample reservoir 13 and stored in the sample reservoir 13. FIG. 12C shows a state in which the sample collection mechanism unit 12 has moved and the area of the area unit 3 is near zero. The sample is in the position indicated by 18 in (c) of FIG. When the sample collection mechanism 12 is further moved in the direction of the arrow 16, the tip of the biosensor electrode component 11 enters the space in the sample reservoir 13 as shown in FIG. The sample 18 that has lost its place due to the narrowing of the portion 13 moves to the sample holding portion 2 by the action of the surfactant in the sample holding portion 2.
[0036]
  At this time, close contact with the skinCurved part15 materials are made elastic, such as rubber, orCurved partIt is possible to eliminate the pain caused by moving the wiper while being in close contact with the skin by making the wiper elastic, for example, made of rubber or the like, at the portion to be contacted with the skin of 15Curved partIt is possible to reliably prevent the sample from entering the gap between 15 and the skin.
[0037]
With this biosensor, a sample holding portion 2 having a width of 0.8 mm, a height of 150 μm, and a depth of 3 mm (capacity of about 0.36 μL) was produced. 1 μL of 0.5% hydroxyethyl cellulose, 1% potassium ferricyanide, and 500 IU / ml aqueous solution was dispensed as a reagent reaction layer to the sample holder 2 and dried at 50 ° C. for 10 minutes. Further, 0.6 μL of 1.0% Triton X-405 aqueous solution was dispensed as a surfactant layer and dried at 40 ° C. for 5 minutes. The diameter r2 of the area part 3 where the sample is arranged was 6 mm, and the length h2 was 24 mm. 0.4 μL, 0.6 μL, 0.9 μL, 1.2 μL, and 1.5 μL of whole blood was gently dropped on the skin, and hemispherical whole blood collection experiments were performed 10 times. It was evaluated by visually observing whether or not whole blood was collected in one sample holder 2. The experimenter had astigmatism and a visual acuity of 0.03, and the distance between the skin where the whole blood was placed and the eyes was about 60 cm. The results are shown in Table 2 (a). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0038]
Furthermore, the same experiment as described above was performed with the whole blood arranged in a hemispherical shape spread on the skin. The results are shown in Table 2 (b). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where the whole blood can be collected only 4 times or less is indicated by ×.
[0039]
Further, the whole blood was divided into three equal parts at 17a, 17b, and 17c in FIG. 2B, and the same experiment as described above was performed. The results are shown in Table 2 (c). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0040]
[Table 2]

As shown in Table 2, there is no difference depending on the state of the sample, that is, whether it is hemispherical, spread, or split. The above results indicate that collection of a very small amount of sample on the skin is well collected even for a person with bad eyes.
[0041]
  Next, a case where the liquid on the skin is collected will be described as a representative example with reference to the drawings. FIG. 3 is a plan view showing the biosensor in the order of its operation steps. As the configuration of this biosensor, the electrode configuration unit 11 having the sample holding unit 2 and itself move to determine the sample collection wire 21 that collects the sample and the initial position of the sample collection wire 21.Fixed part22 is comprised. The sample collection wire 21 can move while sandwiching both sides of the electrode component 11, and its tip isFixed part22 inside. This biosensor has a large area portion 3 for arranging a sample and a sample holding portion 2 as in the second embodiment. The sample holding portion 2 introduces a reagent reaction layer and a sample for quantitative measurement to the sample holding portion 2. A surfactant layer for dispensing is dispensed. The sample moves from the area portion 3 to the sample suction hole 1 and the sample holding portion 2 by the operation described below. Since this biosensor is used in a state of being connected to an apparatus when a sample is collected, it is not necessary to directly have this biosensor, and an operation for collecting a sample is performed by the apparatus.
[0042]
From this, a sample collection method will be described. First, in the wide area part 3 surrounded by the tip part of the electrode structure part 11 and the sample collection wire 21 at the tip of the biosensor connected to the apparatus, there is a sample 5 that is placed on the skin. Move the device.
[0043]
  Next, the sample collection wire 21Fixed partWhen the sample 22 is moved in the direction of the arrow 23 while being in close contact with the skin, the sample 5 advances while being scraped by the sample collection wire 21. FIG. 3B shows a state at the moment when the movement of the sample collection wire 21 is completed. The sample that has lost its destination moves to the sample holder 2 by the action of the surfactant in the sample holder 2.
[0044]
At this time, the material of the sample collection wire 21 to be in close contact with the skin is elastic, for example, rubber or polyethylene terephthalate having a thickness of 200 μm or less which has been subjected to a water repellent treatment in order to move smoothly. Although it is preferable, it is not limited as long as it has elasticity. Further, by making the wiper elastic, for example, made of rubber or the like, at the portion of the sample collection wire 21 that comes into contact with the skin, it is possible to completely eliminate the pain caused by moving while making contact with the skin. In addition, it is possible to reliably prevent the sample from entering the gap between the sample collection wire 21 and the skin.
[0045]
With this biosensor, a sample holding portion 2 having a width of 0.8 mm, a height of 150 μm, and a depth of 3 mm (capacity of about 0.36 μL) was produced. 1 μL of 0.5% hydroxyethyl cellulose, 1% potassium ferricyanide, and 500 IU / ml aqueous solution was dispensed as a reagent reaction layer to the sample holder 2 and dried at 50 ° C. for 10 minutes. Further, 0.6 μL of 1.0% Triton X-405 aqueous solution was dispensed as a surfactant layer and dried at 40 ° C. for 5 minutes. The diameter r3 of the area part 3 where the sample is arranged was 8 mm, and the angle d3 was 270 degrees. 0.4 μL, 0.6 μL, 0.9 μL, 1.2 μL, and 1.5 μL of whole blood was gently dropped on the skin, and hemispherical whole blood collection experiments were performed 10 times. It was evaluated by visually observing whether or not whole blood was collected in one sample holder 2. The experimenter had astigmatism and a visual acuity of 0.03, and the distance between the skin where the whole blood was placed and the eyes was about 60 cm. The results are shown in Table 3 (a). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0046]
Furthermore, the same experiment as described above was performed with the whole blood arranged in a hemispherical shape spread on the skin. The results are shown in Table 3 (b). In addition, the case where it was able to collect | recover whole blood 9 times or more (circle), the case where it was able to collect 5-8 times, (triangle | delta), and the case where it was able to collect only 4 times or less are shown by x.
[0047]
Further, the whole blood was divided into three equal portions at 24a, 24b, and 24c in FIG. 3B, and the same experiment as described above was performed. The results are shown in Table 3 (c). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0048]
[Table 3]

As shown in Table 3, there is no difference depending on the state of the sample, that is, whether it is hemispherical, spread, or split. The above results indicate that collection of a very small amount of sample on the skin is well collected even for a person with bad eyes.
[0049]
As a comparative example, the case of collecting liquid on the skin will be described as a representative example with reference to the drawings. FIG. 4E is a perspective view of the biosensor. In this biosensor, the sample is moved to the sample holder 2 by bringing the sample suction hole 1 into direct contact with the sample. Since this biosensor is used in a state of being connected to an apparatus when a sample is collected, it is not necessary to directly have this biosensor, and an operation for collecting a sample is performed by the apparatus.
[0050]
With this biosensor, a sample holding portion 2 having a width of 0.8 mm, a height of 150 μm, and a depth of 3 mm (capacity of about 0.36 μL) was produced. 1 μL of 0.5% hydroxyethyl cellulose, 1% potassium ferricyanide, and 500 IU / ml aqueous solution was dispensed as a reagent reaction layer to the sample holder 2 and dried at 50 ° C. for 10 minutes. Further, 0.6 μL of 1.0% Triton X-405 aqueous solution was dispensed as a surfactant layer and dried at 40 ° C. for 5 minutes. 0.4 μL, 0.6 μL, 0.9 μL, 1.2 μL, and 1.5 μL of whole blood was gently dropped on the skin, and hemispherical whole blood collection experiments were performed 10 times. It was evaluated by visually observing whether or not whole blood was collected in one sample holder 2. The experimenter had astigmatism and a visual acuity of 0.03, and the distance between the skin where the whole blood was placed and the eyes was about 60 cm. The results are shown in Table 4 (a). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0051]
Furthermore, the same experiment as described above was performed with the whole blood arranged in a hemispherical shape spread on the skin. The results are shown in Table 4 (b). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0052]
Furthermore, whole blood was divided into three equal parts at three locations, and the same experiment as described above was performed. The results are shown in Table 4 (c). In addition, the case where the whole blood can be collected 9 times or more is indicated by ◯, the case where 5 to 8 times can be collected is indicated by Δ, and the case where only 4 times or less can be collected is indicated by ×.
[0053]
[Table 4]

The cause of the failure in the results of the above experiment is that, in Table 4 (a), whole blood is brought into contact with a portion other than the sample suction hole 1, and the whole blood is crushed or attached to the back side of the biosensor. Most of them were trapped. In (b) of Table 4, in addition to the above-mentioned causes, it is due to the inclusion of bubbles despite the good contact. In the case of (c) in Table 4, in this biosensor, only one of the divided blood droplets can be used, which matches the cause of failure in (a) of Table 4. The above results show that it is very difficult for a person with poor eyesight to contact the sample suction hole 1 having a width of 0.8 mm and a height of 150 μm when the sample becomes extremely small.
【The invention's effect】
[0054]
As described above, according to the present invention, even if the sample is very small, even if the sample is not hemispherical and is crushed and spread, or even if the sample is divided into a plurality of samples, all of them can be easily handled. It can be collected by simple operation, and it can be transported to the target position and used.
[Brief description of the drawings]
FIG. 1 is a plan view showing a biosensor according to an embodiment of the present invention in the order of its operation steps.
FIG. 2 is a plan view showing a biosensor according to another embodiment of the present invention in the order of its operation steps.
FIG. 3 is a plan view showing a biosensor according to another embodiment of the present invention in the order of its operation steps.
FIG. 4 is a plan view showing a biosensor according to a conventional technique in the order of its manufacturing steps.
[Explanation of symbols]
  1 Sample suction hole
  2 Sample holder
  3 area part
  4 Measuring device end
  5 samples
  6CurvedPart
  7 Movement direction
  8a Sample location
  8b Sample location
  8c Sample location
  11 Electrode component
  12 Collection mechanism
  13 Sample reservoir
  14 Subskeleton
  15CurvedPart
  16 Direction of movement
  17a Sample location
  17b Sample location
  17c Sample location
  18 samples
  21 Sample collection wire
  22Fixed part
  23 Movement direction
  24a Sample location
  24b Sample location
  24c Sample location
  r1 Dimensions in the biosensor used in Example 1
  h1 Dimensions in the biosensor used in Example 1
  r2 Dimensions in the biosensor used in Example 2
  h2 Dimensions in the biosensor used in Example 2
  r3 Dimensions in the biosensor used in Example 3
  d3 Angle in the biosensor used in Example 3
  31 substrates
  32 Lead part
  33 Lead
  34 Measuring electrode
  35 Counter electrode
  36 Surfactant layer
  38 Cover
  40 Top cover
  41 Metal film
  42 slit

Claims (6)

And skeletal portion having a bay song part,
A connector portion that is connected to the inside of the quantitative device and extends from the curved portion ;
A biosensor comprising an area part surrounded by the skeleton part,
The curved portion includes a sample holding hole and a sample holder having a reagent reaction layer,
When the sample is collected, the biosensor is moved so that the sample on the sample placement surface is in the area portion, and the sample is scraped together in one place by the curved portion,
The biosensor in which the sample collected is introduced and held in the sample holding unit through the sample suction hole . The skeleton is the biosensor of the curved portion and has a wiper with a resilient force to eliminate the gap between the sample placement surface, according to claim 1, wherein. An electrode component having a sample holding part on which a reagent reaction layer is formed;
A sample collecting mechanism that collects samples in one place and that can be moved in whole or in part relative to the electrode component;
With
Wherein said closed space sandwiched by both between the sampling mechanism and the front Symbol electrode forming portion is formed, and samples existing in the closed space, the sampling mechanism is toward the electrode forming portion by moving Te, and introducing before Symbol sample holding portion, the biosensor. The sampling mechanism may have a sample reservoir for storing the samples scraped,
The sample existing in the closed space is stored in the sample storage unit as the sample collection mechanism unit moves toward the electrode configuration unit, and the sample stored in the sample storage unit is stored in the sample storage unit. The biosensor according to claim 3 , wherein the part moves and the tip of the electrode constituent part enters the sample storage part to be introduced into the sample holding part . The sample holding part has a sample suction hole,
The biosensor according to claim 4, wherein the electrode component moves the sample collection mechanism toward the electrode component so that the sample suction hole enters the sample collection mechanism. .   The sample collection mechanism unit is movable relative to the electrode configuration unit, and a sample collection wire for introducing the sample collected to the sample holding unit, a fixing unit for determining an initial position of the sample collection wire, The biosensor according to claim 3, comprising:

Images