JPH0217077B2 - - Google Patents
Info
- Publication number
- JPH0217077B2 JPH0217077B2 JP58204291A JP20429183A JPH0217077B2 JP H0217077 B2 JPH0217077 B2 JP H0217077B2 JP 58204291 A JP58204291 A JP 58204291A JP 20429183 A JP20429183 A JP 20429183A JP H0217077 B2 JPH0217077 B2 JP H0217077B2
- Authority
- JP
- Japan
- Prior art keywords
- chamber
- analytical device
- sample liquid
- sample
- detection cell
- 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 - Lifetime
Links
- 239000000523 sample Substances 0.000 claims description 27
- 239000007788 liquid Substances 0.000 claims description 25
- 238000000502 dialysis Methods 0.000 claims description 19
- 108010093096 Immobilized Enzymes Proteins 0.000 claims description 18
- 238000001514 detection method Methods 0.000 claims description 18
- 238000004458 analytical method Methods 0.000 claims description 17
- 239000012528 membrane Substances 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 238000006911 enzymatic reaction Methods 0.000 claims description 8
- 239000012488 sample solution Substances 0.000 claims description 8
- 239000000758 substrate Substances 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 description 14
- 239000008280 blood Substances 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 11
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- 239000007853 buffer solution Substances 0.000 description 9
- 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 8
- 239000008103 glucose Substances 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 239000000872 buffer Substances 0.000 description 7
- 235000000346 sugar Nutrition 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 210000000601 blood cell Anatomy 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N 4-aminoantipyrine Chemical compound CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 108010015776 Glucose oxidase Proteins 0.000 description 2
- 239000004366 Glucose oxidase Substances 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000009534 blood test Methods 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000004040 coloring Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229940116332 glucose oxidase Drugs 0.000 description 2
- 235000019420 glucose oxidase Nutrition 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000013076 target substance Substances 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 229920000298 Cellophane Polymers 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000009535 clinical urine test Methods 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000012864 cross contamination Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 108010046301 glucose peroxidase Proteins 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Description
【発明の詳細な説明】
本発明は血液や尿等を臨床化学分析するための
新規な分析デバイスに関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel analytical device for clinical chemical analysis of blood, urine, etc.
今日、自動臨床化学分析装置の著しい普及によ
り血液や尿の検査は短時間で正確に行なわれるよ
うになり、臨床分野において大いに貢献してい
る。しかしながら、従来の臨床分析は第１図に示
す様に採血１の後、一定期間静置・凝固し２，３
の血清分離・分注という過程を経て血球分を分離
し、場合によつては更に蛋白質を除去した後、分
析装置に導入して自動分析４すると言う大変に厄
介な作業を必要とし、分析までに手間と時間が掛
りすぎる問題を有している。即ち、特に血球分の
分離には遠心力場を利用した遠心分離機が使用さ
れるが、分離された血液は試料管の底部に血球分
が、又その上部に血清、又は血漿が液体の状態で
存在し、このようにして分離された血清（又は血
漿）をピペツトで吸い上げて分析装置の試料管に
移し換えている。この様な作業は非常に厄介であ
り、緊急を要する血液の検査に間に合わない場合
が多い。 Nowadays, with the remarkable spread of automatic clinical chemistry analyzers, blood and urine tests can be performed accurately in a short time, making a great contribution to the clinical field. However, in the conventional clinical analysis, as shown in Figure 1, after blood collection 1, it is left to stand and coagulate for a certain period of time.
The blood cells are separated through the process of serum separation and dispensing, and in some cases proteins are further removed, which is then introduced into an analyzer for automatic analysis4, which is a very troublesome process. The problem is that it takes too much time and effort. In other words, a centrifuge using a centrifugal force field is used to separate blood cells, but the separated blood has blood cells at the bottom of the sample tube and serum or plasma at the top in a liquid state. The serum (or plasma) thus separated is drawn up with a pipette and transferred to the sample tube of the analyzer. Such work is extremely troublesome, and often results in not being able to complete urgent blood tests in time.
而して、本発明は上記従来の欠点を解消するも
ので、第１図において点線で示すように採血後直
ちに分析でき、静置や血清分離・分注等の作業の
全く不要な新規な分析デバイスを提供することに
目的を有する。 The present invention solves the above-mentioned conventional drawbacks, and provides a novel analysis method that allows blood to be analyzed immediately after blood collection, as shown by the dotted line in FIG. The purpose is to provide devices.
本発明の構成は単一基体内に多孔質の薄い透析
膜により分離された２つの部屋を形成し、第１の
部屋には分析すべき試料液を導入し、第２の部屋
には固定化酵素を充填すると共に透析膜を通過し
た試料液を抽出及び若しくは該試料液と反応する
溶液を注入し、前記第２の部屋に連通して同一基
体内に検出セル部を形成し、前記第２の部屋内で
反応した試料溶液を該検出セル部に導入して所定
の分析を行なうようした臨床分析用分析デバイス
に特徴がある。 The structure of the present invention forms two chambers separated by a porous thin dialysis membrane in a single substrate, the first chamber is where the sample liquid to be analyzed is introduced, and the second chamber is where the immobilized sample is introduced. Filled with an enzyme, extract the sample liquid that has passed through the dialysis membrane, or inject a solution that reacts with the sample liquid, communicate with the second chamber to form a detection cell part in the same base, and The analytical device for clinical analysis is characterized in that a sample solution reacted in the chamber is introduced into the detection cell section and a predetermined analysis is performed.
以下図面に示した実施例に基づき本発明を説明
する。 The present invention will be described below based on embodiments shown in the drawings.
第２図は本発明の主要部を示す縦断面図、第３
図は第２図のＡ−Ａ断面図であり、５は耐薬品性
に優れたガラスやセラミツク等で形成された基体
であり、内部に部屋６，７、及び８が設けられて
いる。第１の部屋６と第２の部屋７との間は薄い
透析膜９で仕切られており、第１の部屋には検査
すべき血液や尿等の試料液が導入口１０から導入
され、検査後の液は排出口１１から排出される。
前記第２の部屋の中には固定化酵素１２が充填さ
れており、透析膜９を通過した試料分子（糖）と
酵素反応する。該第２の部屋内には透析した試料
液の抽出及び若しくは該試料液と化学反応を行な
う緩衝液が導入口１３を介して導入される。前記
固定化酵素は２種又はそれ以上が混ぜた状態で充
填されており、両酵素を媒介にして緩衝液の発色
反応が遂行されるように構成している。前記第２
の部屋内で発色した、又は発色過程の試料液は通
路１４を介して検出セル部８内に導入され、静止
状態に保持される。該検出セル部の上方にはオプ
テイカルフアイバ１５の一端が設置され、その他
端に配置されたレンズ１６及びフイルタ１７を介
して光源１８より所定単波長の光束が導入され、
基体５を通して検出セル部に照射される。該検出
セル部において発色した試料溶液により吸収され
た光束は更に基体を通過してフオトダイオード等
の光検出器１９により検出される。検出の終了し
た試料溶液は排出口２０より排出液槽（図示せ
ず）に廃棄される。第４図は前記第２図及び第３
図に示した分析デバイスＡを使用した分析装置全
体の概略図であり、試料液導入口１０は試料注入
器２１に接続し、該注入器より直接血液が第２図
の第１の部屋６内に注入される。緩衝液導入口１
３は切換え弁２２を介してポンプ２３に接続し、
緩衝液槽２４内の緩衝液が第２の部屋７内に注入
できる。２５は洗浄液槽であり、例えば血液と同
じ塩濃度の0.8％の食塩水が注入してあり、該洗
浄液はポンプ２６により吸い上げられ、切換え弁
２２を介して、或るいは弁２７を介して前記試料
液注入器２１に導入できる。又、デバイスＡの排
出口２０からの廃液は廃液槽２８に貯留される。
光検出器１９の出力は増幅器２９を介して信号処
理回路３０に送られ、適宜処理された後、記録又
は表示装置３１に送られ、分析（検査）結果が表
示される。 Fig. 2 is a vertical sectional view showing the main parts of the present invention;
The figure is a sectional view taken along the line A-A in FIG. 2, and numeral 5 is a base made of glass, ceramic, or the like with excellent chemical resistance, and chambers 6, 7, and 8 are provided inside. The first chamber 6 and the second chamber 7 are separated by a thin dialysis membrane 9, and a sample liquid such as blood or urine to be tested is introduced into the first chamber through an inlet 10, and then the sample liquid for the test is carried out. The remaining liquid is discharged from the discharge port 11.
The second chamber is filled with an immobilized enzyme 12, which undergoes an enzymatic reaction with sample molecules (sugar) that have passed through the dialysis membrane 9. A buffer solution for extracting the dialyzed sample solution and/or performing a chemical reaction with the sample solution is introduced into the second chamber through the inlet 13. The immobilized enzymes are packed in a mixture of two or more types, and the coloring reaction of the buffer solution is carried out through the use of both enzymes. Said second
A sample liquid that has developed a color or is in the process of developing a color in the chamber is introduced into the detection cell section 8 through the passage 14 and kept in a stationary state. One end of the optical fiber 15 is installed above the detection cell section, and a light beam of a predetermined single wavelength is introduced from a light source 18 through a lens 16 and a filter 17 placed at the other end.
The detection cell portion is irradiated through the base 5. The light flux absorbed by the colored sample solution in the detection cell portion further passes through the substrate and is detected by a photodetector 19 such as a photodiode. The sample solution for which detection has been completed is discarded from the discharge port 20 into a discharge liquid tank (not shown). Figure 4 is the same as the above-mentioned Figures 2 and 3.
2 is a schematic diagram of the entire analyzer using the analytical device A shown in FIG. is injected into. Buffer inlet 1
3 is connected to the pump 23 via the switching valve 22,
The buffer in the buffer tank 24 can be injected into the second chamber 7 . Reference numeral 25 denotes a washing liquid tank, into which, for example, 0.8% saline having the same salt concentration as blood is injected. It can be introduced into the sample liquid injector 21. Further, the waste liquid from the discharge port 20 of the device A is stored in a waste liquid tank 28.
The output of the photodetector 19 is sent to a signal processing circuit 30 via an amplifier 29, and after being appropriately processed, is sent to a recording or display device 31, where the analysis (inspection) results are displayed.
以上のようなデバイスを使用した装置におい
て、血液中のグルコースの検査を行なう場合につ
いて説明する。先ず、第２図における透析膜とし
ては数乃至数十μの厚さのセロハンやビニール
系、又はポリカーボネート系の多孔質高分子物質
が選択される。この様な透析膜を用いて区画され
た部屋７内にグルコース オキシデイズ及びペル
オキシデイズを適宜混合した固定化酵素を充填
し、該部屋内にポンプ２３によつて４アミノアン
チピリンを含有した緩衝液を導入しておき、第１
の部屋内に試料液注入器２１から採血した血液を
注入する。この様な状況において、血中の糖、例
えばグルコースは血球に比較して遥かに分子量が
小さいので、該グルコースは前記透析膜９の多数
の小さな孔を通過して第２の部屋７内に浸入す
る。この浸入したグルコースは充填されている固
定化酵素のグルコース オキシデイズと酵素反応
を起しグルコン酸と過酸化水素に分解される。こ
の過酸化水素は同じく部屋７内に固定されたペル
オキシデイズを触媒にして該部屋内の４アミノア
ンチピリンと化学反応を起して発色する。この発
色の程度は過酸化水素の量に比例するので、透析
膜９から浸透してきたグルコースの量に応じた発
色現象が得られ、検体としての血液に応じた比色
測定が可能となる。前記第１の部屋６から第２の
部屋７への分子の浸入、或るいは透析は目的物の
濃度差によるので、初期においては第２の部屋は
グルコースの濃度が０であるので極めて速やかに
グルコースの透析が行なわれる。そして、透析が
進行すると浸入した目的物（グルコース）は固定
化酵素と反応を起し、濃度が低下していくため、
更にその分子は透析が進行する。しかし、透析し
た分子の内反応にあずからない分子は第１の部屋
の濃度と第２の部屋の濃度とが等しくなつた状態
で透析はストツプする。このようにして目的とす
る分子が極めて効果的に第２の部屋に抽出され、
酵素反応を生起して発色現象が進行する。予め設
定した時間経過後、第２の部屋の溶液をポンプ２
３を作動させて検出セル部８内に送り込み、単色
光束を照射してその液体による吸光度の測定を行
なう。測定の結果は記録計又は表示装置３１に記
録される。特定の試料の検査が終了した場合、切
換え弁２２を切換え、又弁２７を開き、ポンプ２
６を作動させて洗浄液を第１の部屋６及び第２の
部屋７内に導入する。この洗浄液としては0.8％
の食塩水が使用されているので、血球の破壊なし
に各部屋内を綺麗に浄化できる。実際の装置では
この食塩水の使用の後、真水による洗浄を行なう
ように構成すると良い。 A case will be described in which a blood glucose test is performed using an apparatus using the above device. First, as the dialysis membrane shown in FIG. 2, a porous polymer material such as cellophane, vinyl, or polycarbonate having a thickness of several to several tens of microns is selected. A room 7 partitioned using such a dialysis membrane is filled with an immobilized enzyme containing an appropriate mixture of glucose oxidase and peroxidase, and a buffer solution containing 4-aminoantipyrine is introduced into the room by a pump 23. The first step is to introduce
The collected blood is injected into the chamber from the sample liquid injector 21. In such a situation, sugar in the blood, such as glucose, has a much smaller molecular weight than blood cells, so the glucose passes through the many small pores of the dialysis membrane 9 and enters the second chamber 7. do. This infiltrated glucose undergoes an enzymatic reaction with glucose oxidase, an immobilized enzyme packed, and is decomposed into gluconic acid and hydrogen peroxide. This hydrogen peroxide causes a chemical reaction with the 4-aminoantipyrine in the chamber 7 using peroxidize fixed in the chamber 7 as a catalyst, and develops a color. Since the degree of color development is proportional to the amount of hydrogen peroxide, a color development phenomenon corresponding to the amount of glucose permeated from the dialysis membrane 9 can be obtained, and colorimetric measurement can be performed according to the blood as a specimen. The infiltration of molecules from the first chamber 6 to the second chamber 7 or dialysis depends on the concentration difference of the target substance, and since the concentration of glucose in the second chamber is 0 at the initial stage, the dialysis is carried out very quickly. Glucose dialysis is performed. As dialysis progresses, the target substance (glucose) that has entered reacts with the immobilized enzyme and its concentration decreases.
Furthermore, the molecule undergoes dialysis. However, the dialysis stops when the concentration of molecules that do not participate in the internal reaction of the dialyzed molecules becomes equal to the concentration in the first chamber and the second chamber. In this way, the target molecules are extracted very effectively into the second chamber,
An enzymatic reaction occurs and the coloring phenomenon progresses. After a preset period of time, pump the solution in the second chamber 2.
3 is activated and sent into the detection cell section 8, and a monochromatic light beam is irradiated to measure the absorbance of the liquid. The results of the measurements are recorded on a recorder or display device 31. When the inspection of a specific sample is completed, switch the switching valve 22, open the valve 27, and turn off the pump 2.
6 is activated to introduce the cleaning liquid into the first chamber 6 and the second chamber 7. This cleaning solution is 0.8%
Since this saline solution is used, each room can be thoroughly purified without destroying blood cells. In an actual apparatus, it is preferable to configure the apparatus to perform washing with fresh water after using this saline solution.
以上説明したような分析デバイスを使用する
と、血球分離−分注−分析（反応）−測定のプロ
セスが単一のチツプ内で全て実行できるので、第
１図において点線で示した採血１から直ちに分析
４へ移行でき、緊急検体の検査に最適である。し
かも、装置は非常に小型になり且つ試料液や緩衝
液等の移動のための機構が不要で、配管も必要な
いので装置が単純化でき、クロスコンタミの問題
も生じない。 When using the analysis device described above, the processes of blood cell separation, dispensing, analysis (reaction), and measurement can all be performed within a single chip, so blood collection 1, shown by the dotted line in Figure 1, can be immediately analyzed. 4, making it ideal for testing emergency specimens. Furthermore, the apparatus is extremely compact, and does not require a mechanism for moving sample liquids, buffer solutions, etc., nor does it require piping, so the apparatus can be simplified and the problem of cross contamination does not occur.
尚、上記透析膜９、固定化酵素及び緩衝液は分
析又は検査する蛋白質の種類に応じて最適なもの
が選択される。 The dialysis membrane 9, immobilized enzyme, and buffer are selected optimally depending on the type of protein to be analyzed or tested.
第５図は本発明の他の実施例であり、第１及び
第２の部屋の形状の例を示すものである。図より
明らかなように、部屋６及び７（６は図示せず）
は蛇行した形状に作られ、効率的に試料液が第２
の部屋に浸透し且つ該浸透した試料液が固定化酵
素と有効に反応するように工夫してある。勿論、
第５図の形状も一例であり、この形状が最良とは
限らない。 FIG. 5 shows another embodiment of the present invention, and shows examples of the shapes of the first and second rooms. As is clear from the figure, rooms 6 and 7 (6 is not shown)
is made in a meandering shape, allowing the sample liquid to flow efficiently into the second
It is designed so that the sample solution permeates into the chamber and the permeated sample solution reacts effectively with the immobilized enzyme. Of course,
The shape shown in FIG. 5 is also an example, and this shape is not necessarily the best.
第６図は本発明の更に他の実施例を示すもの
で、検出手段として比色測定に代えて酸素濃度の
検出手段を使用する場合である。図中第２図と同
符号は同様な構成を示しており、検出セル部８内
には酸素電極３２が挿入されている。前述したよ
うに酵素反応の過程において、過酸化水素が発生
し、該過酸化水素と他の緩衝液と反応する過程で
酸素を放出し、これが溶存酸素として溶液中存在
する。この溶存酸素を酸素電極３２により測定す
ると第２の部屋内で酵素反応を起した目的とする
糖の量が実測できるわけである。 FIG. 6 shows still another embodiment of the present invention, in which oxygen concentration detection means is used instead of colorimetric measurement as the detection means. The same reference numerals as in FIG. 2 indicate the same structure, and an oxygen electrode 32 is inserted into the detection cell portion 8. As mentioned above, hydrogen peroxide is generated during the enzymatic reaction, and during the reaction of the hydrogen peroxide with another buffer, oxygen is released, and this is present in the solution as dissolved oxygen. By measuring this dissolved oxygen using the oxygen electrode 32, it is possible to actually measure the amount of target sugar that has undergone an enzymatic reaction in the second chamber.
第７図は本発明分析デバイスの使用例を示すも
ので、複数個の分析デバイスA1，A2，A3，…を
直列に接続し、異なつた糖（異なつた分子量の分
子）を夫々のデバイスにより順次測定するように
構成したものである。即ち、第１のデバイスの試
料液注入口１０ａから入つた試料は排出口１１ａ
から出て第２のデバイスA2の試料注入口１０ｂ
に入り、該第２のデバイス内に入つた試料液は排
出口１１ｂから第３のデバイスA3の注入口１０
ｃに入るように構成してある。又、夫々のデバイ
スには測定手段として光源１８ａ，１８ｂ，１８
ｃ…及び光検出器１９ａ，１９ｂ，１９ｃ…が設
けられている。勿論、各デバイス内の固定化酵素
の種類や緩衝液の種類、更には透析膜の種類及び
厚さ等は測定する糖の種類に応じて最適なものが
使用されている。 Figure 7 shows an example of the use of the analytical device of the present invention, in which a plurality of analytical devices A 1 , A 2 , A 3 , ... are connected in series, and different sugars (molecules with different molecular weights) are The device is configured to perform measurements sequentially. That is, the sample entered from the sample liquid inlet 10a of the first device is transferred to the outlet 11a.
Sample inlet 10b of the second device A2
The sample liquid that entered the second device flows through the outlet 11b to the inlet 10 of the third device A3 .
It is configured to fit into c. Further, each device is provided with light sources 18a, 18b, 18 as measurement means.
c... and photodetectors 19a, 19b, 19c... are provided. Of course, the type of immobilized enzyme, the type of buffer solution, and the type and thickness of the dialysis membrane in each device are optimally used depending on the type of sugar to be measured.
第８図は更に他の実施例であり、第２図の実施
例では複数の固定化酵素を混合して第２の部屋７
内に充填したが、ここでは２種の固定化酵素を分
離して異なつた部屋内に充填する構成である。即
ち、第２の部屋と検出セル部８との間に第３の部
屋３３を形成し、該部屋内に第２の部屋内の固定
化酵素とは異なる固定化酵素３４を充填してあ
る。そして、第２の部屋７と第３の部屋３３との
間に第２の緩衝液の注入口３５が設けられ、第２
の部屋７内に注入される緩衝液とは異なる緩衝液
が導入される。勿論、必要であれば更に異なつた
固定化酵素の充填された部屋を設けても良い。 FIG. 8 shows still another embodiment, and in the embodiment of FIG. 2, a plurality of immobilized enzymes are mixed and stored in the second chamber 7.
However, in this case, two types of immobilized enzymes are separated and packed into different chambers. That is, a third chamber 33 is formed between the second chamber and the detection cell section 8, and the third chamber 33 is filled with an immobilized enzyme 34 different from the immobilized enzyme in the second chamber. A second buffer solution injection port 35 is provided between the second chamber 7 and the third chamber 33, and a second buffer solution inlet 35 is provided between the second chamber 7 and the third chamber 33.
A different buffer than that injected into chamber 7 is introduced. Of course, if necessary, rooms filled with different types of immobilized enzymes may be provided.
この様な構成とすれば、１３から注入する第１
の緩衝液は第１の部屋６内の試料から所望とする
糖のみを抽出するに最適なものが選択でき、この
ようにして効率的に抽出された糖と固定化酵素と
反応した溶液に発色反応に最適な第２の緩衝液を
第２の注入口３５から注入することが可能とな
り、効率的な測定が行なえる。 With such a configuration, the first injection from 13
The buffer solution can be selected to be optimal for extracting only the desired sugar from the sample in the first chamber 6, and the solution in which the efficiently extracted sugar reacts with the immobilized enzyme develops color. It becomes possible to inject the second buffer solution most suitable for the reaction from the second injection port 35, and efficient measurement can be performed.
第９図は更に他の実施例であり、酵素反応と化
学反応とを組合わせたものである。第２の部屋７
と検出セル部８との間に反応試薬注入口３６を設
け、該注入口より反応試薬を注入して第２の部屋
で生成された酵素反応生成物と化学反応を起さ
せ、その結果生じた発色の程度を吸光度測定する
ように構成してある。 FIG. 9 shows yet another embodiment, which combines an enzymatic reaction and a chemical reaction. second room 7
A reaction reagent inlet 36 is provided between the detection cell section 8 and the reaction reagent injected through the inlet to cause a chemical reaction with the enzymatic reaction product generated in the second chamber. It is configured to measure the degree of color development by absorbance.
以上説明したような構成となせば、採血した血
液を直接分析デバイスで分析でき、従来の様に静
置・凝固や遠心分離器を使用しての血清の分離・
分注等が不要となり、極めて迅速な測定が可能と
なり、緊急検体の検査に有効である。 With the configuration described above, collected blood can be directly analyzed with an analysis device, and serum separation and coagulation using a centrifugal separator can be performed as usual.
It eliminates the need for dispensing, enables extremely rapid measurement, and is effective for testing emergency samples.
第１図は従来の臨床化学分析の流れを示す図、
第２図は本発明の一実施例を示す分析デバイスの
縦断面図、第３図は第２図のＡ−Ａ断面図、第４
図は第２図のデバイスを使用した分析装置の概略
を示す図、第５図乃至第９図は夫々本発明の他の
実施例を示す図である。
５：基体、６：第１の部屋、７：第２の部屋、
８：検出セル部、９：透析膜、１０：試料注入
口、１１：試料排出口、１２：固定化酵素、１
３：緩衝液注入口、１５：グラスフアイバ、１
６：光学レンズ、１７：フイルタ、１８：光源、
１９：光検出器。
Figure 1 shows the flow of conventional clinical chemistry analysis.
FIG. 2 is a longitudinal sectional view of an analytical device showing one embodiment of the present invention, FIG. 3 is a sectional view taken along line A-A in FIG. 2, and FIG.
This figure schematically shows an analysis apparatus using the device shown in FIG. 2, and FIGS. 5 to 9 each show other embodiments of the present invention. 5: Base, 6: First room, 7: Second room,
8: Detection cell part, 9: Dialysis membrane, 10: Sample inlet, 11: Sample outlet, 12: Immobilized enzyme, 1
3: Buffer inlet, 15: Glass fiber, 1
6: optical lens, 17: filter, 18: light source,
19: Photodetector.
Claims (1)
された２つの部屋を形成し、第１の部屋には分析
すべき試料液を導入し、第２の部屋には固定化酵
素を充填すると共に透析膜を通過した試料液を抽
出及び若しくは該試料液と反応する溶液を注入
し、前記第２の部屋に連通して同一基体内に検出
セル部を形成し、前記第２の部屋内で反応した試
料溶液を該検出セル部に導入して所定の分析を行
なうように構成した臨床分析用分析デバイス。 ２ 前記第２の部屋に充填される固定化酵素は複
数種類である特許請求の範囲第１項記載の臨床分
析用分析デバイス。 ３ 前記第２の部屋と検出セル部との間に少なく
とも１個の部屋を形成し、該部屋内に第２の部屋
内に充填した固定化酵素とは異なる酵素を充填し
てある特許請求の範囲第１項記載の臨床分析用分
析デバイス。 ４ 前記第２の部屋と検出セル部との間に酵素反
応生成物と化学反応を起す試薬の注入口を設けた
特許請求の範囲第１項又は第２項記載の臨床分析
用分析デバイス。 ５ 前記第１の部屋から排出された試料液は他の
分析デバイスの第１の部屋内に導入される特許請
求の範囲第１項乃至第４項のいずれかに記載の臨
床分析用分析デバイス。[Claims] 1. Two chambers separated by a porous thin dialysis membrane are formed in a single substrate, the sample liquid to be analyzed is introduced into the first chamber, and the sample liquid to be analyzed is introduced into the second chamber. Filling with the immobilized enzyme and extracting the sample liquid that has passed through the dialysis membrane and/or injecting a solution that reacts with the sample liquid, communicating with the second chamber to form a detection cell part in the same substrate; An analytical device for clinical analysis configured to introduce a sample solution reacted in a second chamber into the detection cell section and perform a predetermined analysis. 2. The analytical device for clinical analysis according to claim 1, wherein the second chamber is filled with a plurality of types of immobilized enzymes. 3. At least one chamber is formed between the second chamber and the detection cell section, and the chamber is filled with an enzyme different from the immobilized enzyme filled in the second chamber. An analytical device for clinical analysis according to Scope 1. 4. The analytical device for clinical analysis according to claim 1 or 2, wherein an inlet for a reagent that causes a chemical reaction with an enzyme reaction product is provided between the second chamber and the detection cell section. 5. The analytical device for clinical analysis according to any one of claims 1 to 4, wherein the sample liquid discharged from the first chamber is introduced into the first chamber of another analytical device.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58204291A JPS6095357A (en) | 1983-10-31 | 1983-10-31 | Analyzing device for crinical analysis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58204291A JPS6095357A (en) | 1983-10-31 | 1983-10-31 | Analyzing device for crinical analysis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6095357A JPS6095357A (en) | 1985-05-28 |
| JPH0217077B2 true JPH0217077B2 (en) | 1990-04-19 |
Family
ID=16488044
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58204291A Granted JPS6095357A (en) | 1983-10-31 | 1983-10-31 | Analyzing device for crinical analysis |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6095357A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0428076U (en) * | 1990-03-09 | 1992-03-05 |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4672511B2 (en) * | 2005-10-05 | 2011-04-20 | 学校法人早稲田大学 | Micro reactor |
| KR100729931B1 (en) | 2006-02-28 | 2007-06-18 | 성균관대학교산학협력단 | Microfluidic Devices for Sample Concentration Amplification |
-
1983
- 1983-10-31 JP JP58204291A patent/JPS6095357A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0428076U (en) * | 1990-03-09 | 1992-03-05 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6095357A (en) | 1985-05-28 |
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