JP5297262B2 - Dispensing instrument verification method and apparatus - Google Patents

Dispensing instrument verification method and apparatus Download PDF

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JP5297262B2
JP5297262B2 JP2009112195A JP2009112195A JP5297262B2 JP 5297262 B2 JP5297262 B2 JP 5297262B2 JP 2009112195 A JP2009112195 A JP 2009112195A JP 2009112195 A JP2009112195 A JP 2009112195A JP 5297262 B2 JP5297262 B2 JP 5297262B2
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晃 服部
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株式会社ユニフレックス
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<P>PROBLEM TO BE SOLVED: To provide a method for inspecting a dispensing implement having high accuracy. <P>SOLUTION: After a detection solution 3A, containing a second coloring matter component, is injected in an absorbance-detecting container 11, in which a standard solution 11A containing a first coloring matter component is housed from the dispensing implement 3 to be detected to prepare a mixed solution, absorbance of the mixed solution is detected. By utilizing the first and second coloring matter components not being reduced by the evaporation phenomenon during the period, the detection value V<SB>s</SB>of the dispensing solution amount of the dispensing implement 3 is calculated, to thereby obtain inspection result of high accuracy. <P>COPYRIGHT: (C)2011,JPO&amp;INPIT

Description

本発明は分注器の検定方法及び装置に関し、特に検定対象である分注器の分注量を、一段と、真値に近く検定できるようにするものである。   The present invention relates to a dispenser verification method and apparatus, and in particular, enables the dispensing amount of a dispenser to be verified to be verified closer to a true value.

1つの試料容器から試料液体を微小量(例えば1〜1000〔μl〕)づつ吸引して1つの取分け容器に取り分けるピペッタや、1つの試料容器から吸引した微小量の同一液体を一定量づつ複数の分注容器に連続分注する分注器や、2つの試料容器から順次異なる液体を吸引して1つの稀釈容器において混合する稀釈器などの、空気置換型の液体吸引器具(これを分注器具と呼ぶ)が従来から用いられている。   A pipetter that draws a sample liquid from one sample container in a minute amount (for example, 1 to 1000 [μl]) and separates it into one sorting container, or a plurality of small amounts of the same liquid sucked from one sample container. Air displacement type liquid aspirator (such as a dispenser that continuously dispenses into a dispenser, or a diluter that aspirates different liquids from two sample vessels and mixes them in one dilution vessel) Is conventionally used.

この種の分注器具は微小量の液体の吸引動作をするものであるから、ユーザは予定された定量の液体を吸引するためには、現実に使用するに先立って、分注器具の分注量を1つづつ検定した後校正する操作をする必要がある(特許文献1〜3参照)。   Since this type of dispensing device performs a suction operation for a minute amount of liquid, the user needs to dispense a predetermined amount of liquid prior to actual use in order to aspirate a predetermined amount of liquid. It is necessary to perform an operation of calibrating after verifying the amounts one by one (see Patent Documents 1 to 3).

特開2008−76393公報JP 2008-76393 A 特開2002−286591公報JP 2002-286591 A 特許第2520852号公報Japanese Patent No. 2520852

微小量の液体を吸引する分注器具の分注量の検定方法としては、1989年に規格化された標準規格ASTM及び2002年に規格化されたISO8655をガイドラインとして、吸引した液体の重量を天秤を用いて計測する重量法が採用されており、この重量法が標準的な基準として分注器具の検定に用いられている。   As a method for verifying the dispensing amount of a dispensing device that aspirates a minute amount of liquid, the standard of ASTM standardized in 1989 and ISO 8655 standardized in 2002 were used as guidelines, and the weight of the sucked liquid was weighed. The gravimetric method is used, and this weight method is used for the verification of dispensing instruments as a standard reference.

この重量法は、吸引した液体の重量を天秤の試料容器に吐出してその重量を測定した後、体積に換算する手法を用いたものである。   This weight method uses a technique in which the weight of the sucked liquid is discharged into a sample container of a balance, the weight is measured, and then converted into a volume.

そこで、重量法に基づく検定は、当該重量の測定過程において、天秤の試料容器に吐出した分注液体が大気中に蒸発するという重大な影響を受けることになるため、実際上分注器具の検定作業を湿度が60〜70〔%〕程度に調整された特別な検定環境の部屋で実施することにより、蒸発量を抑えるような工夫がなされている。   Therefore, the calibration based on the gravimetric method is actually affected by the fact that the dispensed liquid discharged into the sample container of the balance evaporates into the atmosphere in the process of measuring the weight. By performing the work in a room with a special test environment in which the humidity is adjusted to about 60 to 70 [%], a device has been devised to suppress the evaporation amount.

しかしながら、この特別な検定環境条件の下で検定された分注器具であっても、これを用いて液体の分注作業を行う現実の作業環境は必らずしも当該検定環境(すなわち湿度が60〜70〔%〕の)と同じではなく、例えば30〜45〔%〕の湿度程度に低い湿度の環境で分注作業が行なわれるのが普通である。   However, even in the case of a dispensing device that has been certified under this special calibration environment condition, the actual working environment in which the liquid is dispensed using this is not necessarily limited to the calibration environment (i.e., the humidity is low). In general, the dispensing operation is performed in an environment having a humidity as low as, for example, 30 to 45%.

従って、特別な検定環境条件の下で重量法により検定された分注器具であっても、必らずしも検定された分注定量で液体を定量分注できるとは限らない。   Therefore, even with a dispensing instrument that has been tested by the gravimetric method under special test environment conditions, it is not always possible to quantitatively dispense a liquid with the dispensed quantity determined.

本発明は以上の点を考慮してなされたもので、光学計量式の検定手段を用いて分注器具の検定処理を行うことにより、検定した分注器具の現実の作業環境下における分注量が、真値近くになるような検定をすることができるようにした分注器具の検定方法及び装置を提案しようとするものである。   The present invention has been made in consideration of the above points, and the dispensing amount in the actual working environment of the verified dispensing instrument is obtained by performing the verification process of the dispensing instrument using the optical weighing type verification means. However, the present invention intends to propose a method and apparatus for testing a dispensing instrument that can perform a test so as to be close to a true value.

かかる課題を解決するため本発明においては、試料液体を吸引して所定の分注量の分注液を取り分ける分注器具3の検定方法及び装置において、分注液を、基準の波長730[nm]の光を吸光する第1の吸光度特性Q1を有する第1の色素成分を含む基準液11Aが入った吸光度検出容器11に、分注器具3によって吸引されかつ基準の波長730[nm]とは異なる波長520[nm]の光を吸光する第2の吸光度特性Q2を有する第2の色素成分を含む検出液3Aを注入して混合液を作り、当該混合液の吸光度を検出して基準液11Aの吸光度A 及び当該検出した混合液の吸光度A の比と基準液11Aの既知の液量とに基づいて検出液3Aの液量Vを計算することにより、分注器具3の分注量Vの検定値を求めるようにする。 In order to solve such a problem, in the present invention, in the assay method and apparatus of the dispensing instrument 3 that draws a sample liquid and separates a predetermined dispensing amount, the dispensing solution is used with a reference wavelength of 730 [ nm]. ] Is absorbed by the dispensing device 3 into the absorbance detection container 11 containing the first dye component 11A containing the first dye component having the first absorbance characteristic Q1 that absorbs the light and the reference wavelength 730 [ nm ]. second detection solution 3A make the injected liquid mixture containing a dye component, reference fluid 11A detects the absorbance of the mixed solution having a second absorbance characteristics Q2 which absorbs light of a different wavelength 520 [nm] The liquid volume V S of the detection liquid 3A is calculated on the basis of the ratio of the absorbance A B of the liquid and the absorbance A S of the detected mixed liquid and the known liquid volume of the reference liquid 11A. to determine a test value of the amount V S To do.

本発明によれば、検出すべき分注器具から第1の色素成分を含む基準液が入った吸光度検出容器に第2の色素成分を含む検出液を注入して混合液を作ってから、第1及び第2の吸光度検出出力の比を求めて、当該比と基準液の既知量とに基づいて検出液の液量を分注量の検出値として求めることにより、混合液の吸光度を検出するまでの間の蒸発現象によっては第1及び第2の色素成分が減少していないことを利用して、分注器具の分注液量の検出値を求めるようにしたことにより、高い正確度の検定結果を得ることができる。 According to the present invention, since making the mixture by injecting a detection solution containing a second pigment component from the dispensing device to be detected absorbance detecting containers reference fluid enters comprising a first dye component, first The ratio of the first and second absorbance detection outputs is obtained, and the absorbance of the mixed solution is detected by obtaining the amount of the detection solution as a dispensed amount based on the ratio and the known amount of the reference solution. By using the fact that the first and second pigment components are not decreased depending on the evaporation phenomenon until the time point, the detection value of the dispensing liquid amount of the dispensing device is obtained, so that high accuracy can be obtained. The test result can be obtained.

本発明の一実施の形態による分注器具検定装置を示すブロック図である。It is a block diagram which shows the dispensing instrument test | inspection apparatus by one embodiment of this invention. 吸光度検出容器を示す略線的斜視図である。It is a rough-line perspective view which shows an absorbance detection container. 基準液の吸光度特性を示す特性曲線図である。It is a characteristic curve figure which shows the light absorbency characteristic of a reference | standard liquid. 混合液の吸光度特性を示す特性曲線図である。It is a characteristic curve figure which shows the light absorbency characteristic of a liquid mixture. 検定対象分注器具を示す正面図である。It is a front view which shows the test object dispensing instrument. 検定・校正処理手順を示すフローチャートである。It is a flowchart which shows a verification / calibration process procedure. 重量法との比較例の実験データを示す略線図である。It is a basic diagram which shows the experimental data of the comparative example with a gravimetric method. 比較例の実験データとして平均値データを示す図表である。It is a chart which shows average value data as experimental data of a comparative example. 重量法検定における蒸発現象の説明に供する略線図である。It is a basic diagram with which it uses for description of the evaporation phenomenon in a gravimetric method test | inspection. 1000[μl]の分注器具についての蒸発現象の影響の説明に供する略線図である。It is a basic diagram with which it uses for description of the influence of the evaporation phenomenon about a 1000 [microliter] dispensing instrument. 1000[μl]の分注器具についての蒸発現象の影響の説明に供する略線図である。It is a basic diagram with which it uses for description of the influence of the evaporation phenomenon about a 1000 [microliter] dispensing instrument. 100[μl]の分注器具についての蒸発現象の影響の説明に供する略線図である。It is a basic diagram with which it uses for description of the influence of the evaporation phenomenon about a 100 [microliter] dispensing instrument. 10[μl]の分注器具についての蒸発現象の影響の説明に供する略線図である。It is a basic diagram with which it uses for description of the influence of the evaporation phenomenon about the dispensing instrument of 10 [microliters].

以下図面について、本発明の一実施の形態を詳述する。   Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings.

(1)分注器具の検定装置の構成
図1において、1は全体として分注器具検定装置を示し、検定装置本体2と、検定対象分注器具3とで構成されている。
(1) Configuration of Dispensing Instrument Verification Device In FIG. 1, 1 indicates a dispensing instrument verification device as a whole, and includes an verification device body 2 and a verification target dispensing device 3.

検定装置本体2の筐体10には吸光度検出容器11を位置決め収納する検出容器設定溝12が設けられ、光源手段13から射出される白色光源光L1がフィルタ手段14のブランク光フィルタ14A又は検出光フィルタ14Bを透過して吸光度検出容器11に入射され、当該吸光度検出装置11を透過した透過光L2が光電変換手段15に入射するようになされている。   The casing 10 of the verification apparatus main body 2 is provided with a detection container setting groove 12 for positioning and storing the absorbance detection container 11, and the white light source light L1 emitted from the light source means 13 is detected by the blank light filter 14A of the filter means 14 or the detection light. The transmitted light L2 that has passed through the filter 14B and entered the absorbance detection container 11 and passed through the absorbance detection device 11 is incident on the photoelectric conversion means 15.

吸光度検出容器11は、図2に示すように、円筒状の透明ガラス容器によって構成され、白色光源光L1から図3において吸光度曲線Q1で示すように、所定の波長(この実施の形態の場合730〔nm〕の波長)を吸光する青色の色素成分を含む基準液11Aが予め決められた基準液量だけ注入した状態で用意されている。 As shown in FIG. 2, the absorbance detection container 11 is constituted by a cylindrical transparent glass container. As shown by an absorbance curve Q1 in FIG. 3 from the white light source light L1, the absorbance detection container 11 has a predetermined wavelength (730 in this embodiment). A reference solution 11A containing a blue pigment component that absorbs [nm] wavelength) is prepared in a state where a predetermined reference solution amount is injected.

かかる構成の吸光度検出容器11は、検出容器設定溝12内に設定されたとき、上側端に設けられた分注口11Bを筐体10の外側に露出する状態に保持され、これにより分注口11Bに対して、当該検定対象分注器具3が分注液として吸引して来た検出液3Aを吸光度検出容器11内に注入できるようになされている。 When the absorbance detection container 11 having such a configuration is set in the detection container setting groove 12, the dispensing port 11B provided at the upper end is held in a state of being exposed to the outside of the housing 10, thereby the dispensing port. In contrast to 11B, a detection liquid 3A sucked as a dispensing liquid by the assay target dispensing instrument 3 can be injected into the absorbance detection container 11.

検出液3Aは、基準液11Aの色素成分(青色)とは異なる吸光波長(この実施の形態の場合520〔nm〕)の赤色の色素成分を含んでいる。   The detection liquid 3A includes a red dye component having an absorption wavelength (520 [nm] in this embodiment) different from the dye component (blue) of the reference liquid 11A.

かくして吸光度検出容器11は、検定対象分注器具3から検出液3Aを注入されたとき、これを基準液11Aと混合することにより、図4に示すように、基準液11Aの色素成分に基づく吸光度曲線Q1に加えて、当該基準液11Aの吸光度曲線Q1(波長730〔nm〕)の波長位置より離れた波長位置に検出液3Aの吸光度曲線Q2(波長520〔nm〕)が生ずるような吸光度特性を呈することになる。   Thus, when the detection liquid 3A is injected from the assay-target dispensing device 3, the absorbance detection container 11 mixes it with the reference liquid 11A, so that the absorbance based on the dye component of the reference liquid 11A is obtained as shown in FIG. In addition to the curve Q1, the absorbance characteristic such that the absorbance curve Q2 (wavelength 520 [nm]) of the detection solution 3A is generated at a wavelength position away from the wavelength position of the absorbance curve Q1 (wavelength 730 [nm]) of the reference solution 11A. Will be presented.

フィルタ手段14は、ブランク光フィルタ14A及び検出光フィルタ14Bを有し、吸光度検出容器11に基準液11Aだけが入っている状態のとき、フィルタ切換器21によって切換動作される回転機構21Aによってブランク光フィルタ14Aを光源光L1の透過軸線上に挿入することにより、図3に示す基準液の吸光度曲線Q1の光成分だけを取り出して吸光度検出容器11に入射させる。   The filter means 14 includes a blank light filter 14A and a detection light filter 14B. When only the reference liquid 11A is contained in the absorbance detection container 11, the filter means 14 performs blank light by a rotating mechanism 21A that is switched by the filter switch 21. By inserting the filter 14A on the transmission axis of the light source light L1, only the light component of the absorbance curve Q1 of the reference solution shown in FIG. 3 is taken out and made incident on the absorbance detection container 11.

これに対して吸光度検出容器11に対して検定対象分注器具から検出液3Aが注入されて基準液11Aと混合された状態において、フィルタ手段14はフィルタ切換器21の回転機構21Aによって検出光フィルタ14Bを光源光L1の透過軸線上に介挿することにより、図4の検出液3Aの吸光度曲線Q2を含む光成分だけを抽出して吸光度検出容器11に入射させる。 On the other hand, in the state in which the detection liquid 3A is injected from the verification target dispensing device 3 into the absorbance detection container 11 and mixed with the reference liquid 11A, the filter means 14 detects the detection light by the rotation mechanism 21A of the filter switch 21. By inserting the filter 14B on the transmission axis of the light source light L1, only the light component including the absorbance curve Q2 of the detection liquid 3A in FIG. 4 is extracted and made incident on the absorbance detection container 11.

かくして吸光度検出容器11から透過する透過光L2は、ブランク光フィルタ14Aが介挿されているとき図3の基準液11Aの吸光度曲線Q1の光成分を含む透過光L2が光電変換手段15に入射することにより、光電変換手段15はその吸光度Aを表す検出出力S1を出力し、これをマイクロコンピュータ構成の中央処理ユニット(CPU)25に供給する。 Thus, the transmitted light L2 transmitted from the absorbance detection container 11 is incident on the photoelectric conversion means 15 when the blank light filter 14A is interposed, including the light component of the absorbance curve Q1 of the reference liquid 11A in FIG. it allows the photoelectric conversion unit 15 outputs the detection outputs S1 representing the absorbance a B, and supplies it to the central processing unit (CPU) 25 of the microcomputer configuration.

これに対して基準液11Aに検出液3Aが混合された状態において吸光度検出容器11を透過する透過光Lが光電変換手段15に入射されたとき、光電変換手段15は図4の検出液の吸光度曲線Q2の吸光度Aに対応する検出出力S1を出力することにより、これをCPU25に供給をする。 When the transmitted light L 2 passing through the photometric detection chamber 11 in a state where the reference solution 11A is detected liquid 3A mixed hand is incident on the photoelectric conversion unit 15, the photoelectric conversion unit 15 of the detection solution 4 by outputting a detection output S1 corresponding to the absorbance a S of the absorbance curve Q2, to supply it to the CPU 25.

CPU25は次式   CPU25 is the following formula

Figure 0005297262
Figure 0005297262

に基づいて検出液3Aの注入量Vを演算し、当該演算結果をシステムバス26を介して表示手段27に検定値として表示する。 The injection amount V S of the detection liquid 3A is calculated based on the above, and the calculation result is displayed as a test value on the display means 27 via the system bus 26.

(1)式は、検出液3Aの注入量Vは、基準液11Aの液量Vに対して基準液11Aの吸光度Aに対する検出液3Aの吸光度Aとの比率を乗算した値として求めることができることを表している。 Equation (1) indicates that the injection volume V S of the detection liquid 3A is a value obtained by multiplying the liquid volume V B of the reference liquid 11A by the ratio of the absorbance A S of the detection liquid 3A to the absorbance A B of the reference liquid 11A. It represents what can be determined.

また、基準液11Aの吸光度Aに対する検出液3Aの吸光度Aの比は、基準液11Aに対する検出液3Aの稀釈度を表していることから、検出液3Aの注入量Vは、予め吸光度検出容器11に入れられていた基準液11Aの液量に対する検出液3Aの注入量の比として決めることを表している。 The ratio of the absorbance A S of the detection solution 3A to the absorbance A B of the reference solution 11A, since it represents the dilution of the detection liquid 3A for the reference solution 11A, the injection amount V S of the detection fluid 3A is previously absorbance This represents that the ratio is determined as the ratio of the injection amount of the detection liquid 3A to the liquid amount of the reference liquid 11A that has been placed in the detection container 11.

この実施の形態の場合、検定対象分注器具3は図5に示すように、先細りの円筒形状を有する機器本体部31A内にピストン駆動部31Bによってピストン動作するピストン部31Cが設けられ、ユーザが指当て部31Dを指で挟んで他の指で吸引操作部31Eを下方に押込み操作したとき、当該押込み力を伝達シャフト部31Fがピストン駆動部31Bに伝達することにより、ピストン部31Cを下方にピストン動作させる。   In the case of this embodiment, as shown in FIG. 5, the test object dispensing instrument 3 is provided with a piston portion 31 </ b> C in which a piston is operated by a piston drive portion 31 </ b> B in a device main body portion 31 </ b> A having a tapered cylindrical shape. When the finger operation part 31E is pushed downward with another finger while the finger rest part 31D is sandwiched between fingers, the transmission shaft part 31F transmits the pushing force to the piston drive part 31B, thereby moving the piston part 31C downward. Operate the piston.

このときピストン部31Cは下方端部に連結された円錐環状の吸引部31Gを通してその先端に嵌め込まれたチップ部31Hを通して吸引部31G内の空気を下方に吐出させるようになされている。   At this time, the piston portion 31C is configured to discharge the air in the suction portion 31G downward through the tip portion 31H fitted at the tip thereof through the conical annular suction portion 31G connected to the lower end portion.

この状態においてユーザが吸引操作部31Eに対する押圧力を緩めると、ピストン駆動部31Bのスプリング動作によってピストン部31Cを上方にピストン動作させることにより、吸引部31Gがチップ部31Hの空気を内部に吸引することにより、チップ部31Hの先端から分注すべき液体をチップ部31H内に吸引する。   In this state, when the user loosens the pressing force on the suction operation portion 31E, the suction portion 31G sucks the air in the tip portion 31H into the piston portion 31C by moving the piston portion 31C upward by the spring action of the piston drive portion 31B. Thus, the liquid to be dispensed from the tip of the tip portion 31H is sucked into the tip portion 31H.

かくして検定対象分注器具3は分注すべき液体を試料容器から吸引して分注器具検定装置1(図1)の吸光度検出容器11に検出液3Aとして吐出することにより、検定対象分注器具3に予め予定されている分注量の検出液3Aを検定装置本体2に供給し、これにより当該分注液量の検定処理が行われる。   Thus, the verification object dispensing instrument 3 sucks the liquid to be dispensed from the sample container and discharges it as the detection liquid 3A to the absorbance detection container 11 of the dispensing instrument verification apparatus 1 (FIG. 1), thereby the verification target dispensing instrument. 3 is supplied to the verification apparatus main body 2 with a predetermined amount of the detection liquid 3A scheduled in advance, whereby the verification of the amount of the liquid distribution is performed.

以上の構成において、CPU25は入力手段35から検定・校正処理の実行命令が与えられたとき、図6に示す検定・校正処理手順RT1に入って、ステップSP1において検出容器設定溝12に基準液11Aが入れられた吸光度検出容器11が設定されるのを待ち受ける。   In the above configuration, the CPU 25 enters the verification / calibration processing procedure RT1 shown in FIG. 6 when an execution command for verification / calibration processing is given from the input means 35, and in step SP1, the reference solution 11A is placed in the detection container setting groove 12. It waits for the absorbance detection container 11 in which is placed to be set.

当該吸光度検出容器11が設定されたことを確認すると、CPU25は、次のステップSP2に移って制御手段36からフィルタ切換器21に切換制御信号S11を与えることにより、フィルタ手段14のブランク光フィルタ14Aを光源光L1の透過光路に設定すると共に、次のステップSP3において制御手段36から発光制御信号S12を光源手段13に与えることにより白色光源光L1を射出させる。   When the CPU 25 confirms that the absorbance detection container 11 has been set, the CPU 25 moves to the next step SP2 to give a switching control signal S11 from the control means 36 to the filter switching device 21, whereby the blank optical filter 14A of the filtering means 14 is obtained. Is set as the transmission light path of the light source light L1, and the light source control unit S provides the light emission control signal S12 to the light source means 13 in the next step SP3, thereby emitting the white light source light L1.

このときブランク光フィルタ14Aは吸光度検出容器11内に入っている基準液11Aに対する吸光度曲線Q1(図3)の光成分を光源光L1から抽出して吸光度検出容器11の基準液11Aを透過する透過光L2を生じさせることにより、光電変換手段15が当該基準液11Aの吸光度Aを表す検出出力S1を送出し、CPU25はこれをステップSP4において内部のメモリに取り込む。 At this time, the blank light filter 14A extracts the light component of the absorbance curve Q1 (FIG. 3) with respect to the reference liquid 11A contained in the absorbance detection container 11 from the light source light L1, and transmits through the reference liquid 11A in the absorbance detection container 11. by causing the light L2, the photoelectric conversion unit 15 sends a detection output S1, the absorbance a B of the reference liquid 11A, CPU 25 takes in this internal memory in step SP4.

続いてCPU25は、ステップSP5に移って制御手段36からフィルタ切換器21に対して切換制御信号S11を与えることにより検出光フィルタ14Bを光源光L1の透過光路に設定した後ステップSP6において吸光度検出容器11に対して検定対象分注器具3から検出液3Aが注入されるのを待ち受ける。   Subsequently, the CPU 25 moves to step SP5 and sets the detection light filter 14B in the transmission light path of the light source light L1 by giving the switching control signal S11 from the control means 36 to the filter switch 21 and then in step SP6 the absorbance detection container. 11 waits for the detection liquid 3A to be injected from the test subject dispensing device 3.

やがて検出液3Aが吸光度検出容器11に注入されることにより吸光度検出容器11内の混合液の色が変わったとき、CPU25は、検出液3Aの吸光度曲線Q2の成分が透過光L2に得られることによって、光電変換手段15が対応する検出出力S2を発生することにより、CPU25は次のステップSP7に移って当該検出液の吸光度Aを内部の記憶メモリに取り込む。 When the detection liquid 3A is eventually injected into the absorbance detection container 11 and the color of the liquid mixture in the absorbance detection container 11 changes, the CPU 25 obtains the component of the absorbance curve Q2 of the detection liquid 3A in the transmitted light L2. by, by generating a detection output S2 of the photoelectric conversion unit 15 corresponding, CPU 25 is moved to the next step SP7 taking the absorbance a S of the detection fluid in an internal storage memory.

かくして基準液11Aについての波長730〔nm〕における吸光度Aと、波長520〔nm〕における吸光度Aが得られたことにより、CPU25は、ステップSP8において上述の(1)式を演算することにより検出液3Aの注入量を算出してステップSP9において当該検出液の注入量を表示手段27に表示することによりユーザに知らせる。 Thus the absorbance A B at a wavelength of 730 [nm] for the reference solution 11A, by absorbance A S was obtained at a wavelength of 520 [nm], CPU 25, by calculating the equation (1) at step SP8 The injection amount of the detection liquid 3A is calculated, and the injection amount of the detection liquid is displayed on the display means 27 in step SP9 to notify the user.

この後ステップSP10において光源手段13を消灯することにより、CPU25は吸光度検出容器11に検出液3Aを注入した検定対象分注器具3に対する検定処理を終了する。   Thereafter, by turning off the light source means 13 in step SP10, the CPU 25 ends the verification process for the verification target dispensing instrument 3 in which the detection liquid 3A is injected into the absorbance detection container 11.

その後、ユーザはステップSP11において表示手段27の表示に基づいて、検定対象分注器具3(図5)のピストン駆動部31Bのピストン量を調整することにより当該検定対象分注器具3の校正を必要に応じて行い、かくしてCPU25は、次のステップSP12において当該検定・校正処理手順RT1を終了する。   Thereafter, the user needs to calibrate the verification target dispensing instrument 3 by adjusting the piston amount of the piston drive unit 31B of the verification target dispensing instrument 3 (FIG. 5) based on the display on the display means 27 in step SP11. Thus, the CPU 25 ends the verification / calibration processing procedure RT1 in the next step SP12.

以上の構成によれば、検定対象分注器具3(図5)においてチップ部31Hに吸引されて吸光度検出容器11に注入されることにより分注された検出液3Aは、当該分注操作の間に、色素成分が蒸発することはないので、蒸発現象の影響を受けることなく、検出液3Aの分注液量の検定をすることができる。   According to the above configuration, the detection liquid 3A dispensed by being sucked into the tip portion 31H and injected into the absorbance detection container 11 in the test-target dispensing instrument 3 (FIG. 5) is applied during the dispensing operation. In addition, since the dye component does not evaporate, the amount of the dispensed liquid of the detection liquid 3A can be tested without being affected by the evaporation phenomenon.

因に、図1の分注器具検定装置1による分注操作の間に、基準液11A及び検出液3Aに含まれている色素成分は原理的に周囲の湿度に起因して蒸発が生ずることはないような光学計量方式によって検定をすることができるので、例え当該検定操作を分注作業を行う現実の作業環境において、例えば30〜45〔%〕程度の十分に低い湿度の環境で行なわれたとしても、当該検定結果に検定誤差が混入することなく安定な検定結果を得ることができる。   Incidentally, during the dispensing operation by the dispensing instrument verification apparatus 1 in FIG. 1, the pigment component contained in the reference liquid 11A and the detection liquid 3A is in principle evaporated due to the ambient humidity. Because it is possible to perform the verification by an optical weighing method, the verification operation is performed in a sufficiently low humidity environment, for example, about 30 to 45% in an actual working environment in which dispensing work is performed. However, it is possible to obtain a stable test result without introducing a test error into the test result.

このような効果は以下に述べる重量法による検定結果との比較例によって明確に裏付けられる。   Such an effect is clearly supported by a comparative example with the results of the gravimetric assay described below.

(2)重量法との比較例
図7及び図8は、分注液体の蒸発に関して、重量法の検定結果と、上述の実施の形態の構成による検定結果との間の、実験結果の比較例を示すものである。
(2) Comparative Example with Gravimetric Method FIG. 7 and FIG. 8 are comparative examples of experimental results between the calibration result of the gravimetric method and the verification result according to the configuration of the above-described embodiment regarding the evaporation of the dispensing liquid. Is shown.

当該実験条件は、検定環境における湿度を60〔%〕、45〔%〕及び30〔%〕とし、図5に示す検定対象分注器具3として手動ピペッタを用いて、重量法と、上述の構成の光学計量方式とで、それぞれ10ポイントの測定を3回づつ行った。   The experimental conditions are that the humidity in the test environment is 60 [%], 45 [%] and 30 [%], a manual pipettor is used as the test subject dispensing instrument 3 shown in FIG. In each of the optical weighing methods, 10 points were measured three times each.

正確度と精密度の比較論を重点に考慮するため、ピペッタの直線性などは特に論点から除外した。   In order to emphasize the comparative theory of accuracy and precision, pipetter linearity was specifically excluded from the discussion.

ピペッタとして、1000〔μl〕、100〔μl〕及び10〔μl〕を、現在ピペッタを校正する際に多用されているように、湿度60〔%〕において校正したピペッタを用いた。   As pipetters, 1000 [μl], 100 [μl] and 10 [μl] were used, which are calibrated at a humidity of 60 [%], as currently used when calibrating the pipettor.

蒸発値の大きさを確認するために、実質的な蒸発量の補正は行なわずに実験データを取った。   In order to confirm the magnitude of the evaporation value, experimental data was taken without correcting the substantial evaporation amount.

実験者は、個人偏差を考慮して1名で行った。   The experimenter was performed by one person in consideration of individual deviation.

図7及び図8において、各実験における10ポイントの実験結果のばらつきの大きさを1つのバブルの大きさによって表しており、その中心点が平均値として当該バブルの正確度を表している。   7 and 8, the magnitude of the variation of the 10-point experimental results in each experiment is represented by the size of one bubble, and the center point represents the accuracy of the bubble as an average value.

図7及び図8の第1のデータDT1は、1000〔μl〕のピペッタを用いて1000〔μl〕の分注液を採取した場合の実験データを表す。   The first data DT1 in FIG. 7 and FIG. 8 represents experimental data when a dispensing solution of 1000 [μl] is collected using a 1000 [μl] pipettor.

また第2の実験データDT2は、1000〔μl〕のピペッタを用いて500〔μl〕の分注液を採取した場合の実験データを示す。   The second experimental data DT2 shows experimental data when a 500 [μl] dispensing solution is collected using a 1000 [μl] pipettor.

以下同様にして第3及び第4の実験データDT3及びDT4は100〔μl〕のピペッタを用いて100〔μl〕及び10〔μl〕の分注液を採取した実験例を示すと共に、第5及び第6の実験データDT5及びDT6は、10〔μl〕のピペッタを用いて10〔μl〕及び1〔μl〕の分注液を採取した実験例を示す。   Similarly, the third and fourth experimental data DT3 and DT4 show experimental examples in which 100 [μl] and 10 [μl] dispensing solutions were collected using a 100 [μl] pipettor. The sixth experimental data DT5 and DT6 show experimental examples in which 10 [μl] and 1 [μl] dispensing solutions were collected using a 10 [μl] pipettor.

図7及び図8の実験例において、第1に確認されたのは1000〔μl〕から1〔μl〕までの分注液量に亘って、全ての湿度において重量法の値が上述の光学計量方式より低い正確度になっている点である。   In the experimental examples of FIG. 7 and FIG. 8, the first thing to be confirmed is that the gravimetric value is the above-mentioned optical measurement at all humidity over a dispensed amount from 1000 [μl] to 1 [μl]. The accuracy is lower than the method.

これは、上述の実施の形態のような光学計量方式の場合には色素成分の蒸発が発生しないのに対して、重量法の場合には全ての実験結果において天秤上の蒸発が検定値を引き下げていることを表している。   This is because the evaporation of the pigment component does not occur in the case of the optical weighing method as in the above-described embodiment, whereas the evaporation on the balance lowers the calibration value in all the experimental results in the case of the gravimetric method. It represents that.

因に、光学計量方式において用いる色素は蒸発しないために、分注した時点での分注液量がそのままの値として表われたものと解し得る。   Incidentally, since the dye used in the optical measurement method does not evaporate, it can be understood that the amount of the dispensed liquid at the time of dispensing is expressed as it is.

また精密度については、バブルグラフで直径の大きさでばらつきの大きさを表しているように、特に分注液量が微小な分注液について、重量法における検定結果は精密度が低いことが読み取れる。   As for the accuracy, as shown in the bubble graph, which shows the size of the variation in diameter, the accuracy in the gravimetric assay results is low, especially for dispensed liquids with a small volume. I can read.

重量法による検定において正確度が低いのは、図9に示すように、重量法検定において、ピペッタのような検定対象分注器具3を用いて天秤上に分注液を分注する操作をする間に生ずる分注液の蒸発現象が原因であると考えられる。   As shown in FIG. 9, the accuracy of the calibration by the gravimetric method is low, as shown in FIG. 9, in the gravimetric assay, an operation of dispensing the dispensing solution on the balance using the dispensing device 3 to be assayed such as a pipetter. This is thought to be due to the evaporation phenomenon of the dispensed liquid occurring in the meantime.

すなわち、図9(A)に示すように検定対象分注器具3によって試料容器41内の試料液体42をチップ部31Hに分注液43として吸引操作をして、図9(B)及び(C)に示すように天秤44のサンプル容器45に取り分ける操作をする間において、検定対象分注器具3はチップ部31Hに分注液43を吸引する際に、チップ部31H内に生ずる負圧によって吸引した分注液43を内部蒸発させる。   That is, as shown in FIG. 9 (A), the sample liquid 42 in the sample container 41 is sucked into the tip part 31H as the dispensing liquid 43 by the test object dispensing instrument 3, and the liquids shown in FIGS. During the operation of separating the sample container 45 of the balance 44 as shown in FIG. 3), the verification target dispensing device 3 sucks the dispensing liquid 43 into the tip portion 31H due to the negative pressure generated in the tip portion 31H. The dispensed liquid 43 is evaporated internally.

このように「内部蒸発現象」(これをEIP/Evaporation Inside Pipetterと呼ぶ)が生ずると、分注液43が気化することにより液体の体積が800倍前後の体積に膨張するために、チップ部31H内の当該膨張による圧力によって吸引量が小さくなる結果を生ずる。   When the “internal evaporation phenomenon” (referred to as EIP / Evaporation Inside Pipetter) occurs in this way, the liquid 43 expands to a volume of about 800 times due to vaporization of the dispensing liquid 43, so that the tip portion 31H As a result, the suction amount is reduced by the pressure due to the expansion.

この検定対象分注器具3のチップ31Hにおける分注液43の吸引による生ずる内部蒸発現象(EIP)は、図9(A)〜(C)の操作をしている間、すわなち試料吸引から排出するまでの間で生じている。   The internal evaporation phenomenon (EIP) caused by the suction of the dispensing liquid 43 in the tip 31H of the test object dispensing instrument 3 is, in other words, from the sample suction during the operation of FIGS. 9 (A) to (C). It occurs until it is discharged.

重量法検定においては、検定対象分注器具3によって吸引により取り分けられた分注液43は、図9(D)に示すように、サンプル容器45内に排出され、これにより天秤44は排出された分注液43の重量を測定する。   In the gravimetric assay, the dispensing solution 43 separated by suction by the assay-target dispensing device 3 is discharged into the sample container 45 as shown in FIG. 9D, and the balance 44 is thereby discharged. The weight of the dispensing solution 43 is measured.

ところが、当該天秤44上のサンプル容器45に検定対象分注器具3のチップ部31Hから分注液43が排出されると、当該分注液43はサンプル容器45から外気に蒸発できる状態になるため、「天秤上での蒸発現象」(これをEOB/Evaporation On Balanceと呼ぶ)という蒸発現象の発生が避けられない。   However, when the dispensing liquid 43 is discharged from the tip portion 31H of the verification target dispensing device 3 to the sample container 45 on the balance 44, the dispensing liquid 43 can be evaporated from the sample container 45 to the outside air. The occurrence of an evaporation phenomenon called “evaporation phenomenon on a balance” (this is called EOB / Evaporation On Balance) is inevitable.

このような検定操作時に生ずる天秤上での蒸発は、検定対象分注器具3によって取り分けられた分注液43の分注液量の大小によらず発生するが、分注液量が微小量である場合には、検定結果における正確度の誤差に大きく影響する。   The evaporation on the balance that occurs during the calibration operation occurs regardless of the amount of the dispensing solution 43 separated by the dispensing device 3 to be assayed, but the dispensing amount is very small. In some cases, it greatly affects the accuracy error in the test results.

このような天秤上での蒸発現象による検定正確度に対する影響は、図7及び図8の重量法との比較例において明確に読み取ることができる。   The influence of the evaporation phenomenon on the balance on the verification accuracy can be clearly read in the comparative example with the gravimetric method shown in FIGS.

図7及び図8の実験結果から見て、重量法における検定結果は天秤上での蒸発現象(EOB)の影響を受けて、光学計量方式の検定結果に対して検定の正確度がいずれの分注量についても低く出ている。   From the experimental results shown in FIGS. 7 and 8, the gravimetric test results are affected by the evaporation phenomenon (EOB) on the balance. The dosage is also low.

これに対して、上述の実施の形態による光学計量方式の分注器具検定装置1を用いた場合には、基準液11A(図2)に含まれている色素成分量と、検定対象分注器具3によって吸引された検出液3Aに含まれている色素成分量は、蒸発現象によって色素成分量が少なくなるような現象は生じない。   On the other hand, when the optical metering type dispensing instrument verification device 1 according to the above-described embodiment is used, the amount of the dye component contained in the reference liquid 11A (FIG. 2) and the verification target dispensing instrument. The amount of the dye component contained in the detection liquid 3A sucked by 3 does not cause a phenomenon that the amount of the dye component decreases due to the evaporation phenomenon.

従って、図9(D)について上述した天秤上での蒸発現象(EOB)は、分注液の重量の減少として直接に検定結果の正確度の低下を生じさせるのに対して、このような検定の正確度の低下の原因は、色素成分量に基づく吸光度の比較による分注液体の分注量の検定には生じることはない。   Accordingly, the evaporation phenomenon (EOB) on the balance described above with reference to FIG. 9D directly reduces the accuracy of the test result as a decrease in the weight of the dispensing solution, whereas such a test. The cause of the decrease in accuracy does not occur in the assay of the dispensed liquid amount by comparing the absorbance based on the amount of the dye component.

このことは、図7の重量法との比較例の実験結果から明確に読み取り得る。   This can be clearly read from the experimental results of the comparative example with the gravimetric method of FIG.

光学計量方式においても内部蒸発現象(EIP)の影響を受けることは、図10及び図11によって明らかに読み取り得る。   It can be clearly read from FIGS. 10 and 11 that the optical metering system is also affected by the internal evaporation phenomenon (EIP).

図10は図7のうち、1000〔μl〕の検定対象分注器具3についての検定データDT1及びDT2を拡大して示すと共に、図11は図10のうち、光学計量方式のうち、湿度30〔%〕における実験データの描写を省略することにより、その背後にある重量法による実験データを見ることができるようにしたものである。   FIG. 10 is an enlarged view of the test data DT1 and DT2 for 1000 [μl] of the test target dispensing device 3 in FIG. 7, and FIG. 11 is a diagram of FIG. By omitting the depiction of the experimental data in [%], the experimental data by the gravimetric method behind it can be seen.

図10及び図11によれば、重量法及び光学計量方式のいずれについても、内部蒸発現象(EIP)に基づいて、湿度が60〔%〕、45〔%〕、30〔%〕となるに従って正確度が低下していく傾向があると共に、天秤上での蒸発現象(EOB)に基づいて、当該天秤上の蒸発現象がない光学計量方式の検定結果の正確度が高くなっていることが分かる。   According to FIGS. 10 and 11, both the gravimetric method and the optical weighing method are accurate as the humidity becomes 60%, 45%, and 30% based on the internal evaporation phenomenon (EIP). It can be seen that the accuracy of the test result of the optical weighing method without the evaporation phenomenon on the balance is high based on the evaporation phenomenon (EOB) on the balance.

また、60〔%〕湿度の重量法に基づく検定値が30〔%〕湿度の光学計量方式の検定値の近くに表れている。   Further, the test value based on the weight method of 60% humidity appears near the test value of the optical measurement method of 30% humidity.

このことは現象として近似しているのが明らかであるが、バリデーションを必要とする場合の検定値とすると、60〔%〕と30〔%〕の湿度差に理論上の整合性がないことが理解できる。   It is clear that this is approximated as a phenomenon, but if it is a test value when validation is required, the humidity difference between 60% and 30% is not theoretically consistent. Understandable.

蒸発補正のない60〔%〕湿度の重量法の検定は、実際の30〔%〕台湿度下の分注作業現場で起こる正確度を補償できるものではなく、また正確度の許容値の判断を狂わせる結果になっている。   The 60% humidity gravimetric test without evaporation correction does not compensate for the accuracy that occurs at the actual dispensing site under 30% humidity, and determines the accuracy tolerance. The result is crazy.

図12及び図13は、100〔μl〕及び10〔μl〕の分注器具についての実験結果を拡大して示したもので、両方共に、湿度による差が生じている。   FIG. 12 and FIG. 13 are enlarged views of experimental results for 100 [μl] and 10 [μl] dispensing instruments, both of which have a difference due to humidity.

また分注量が小さくなればなるほど蒸発現象を受ける重量法に精密度の低下が見られ(1つのバブルの直径が大きくなっている)、重量法による測定による限界が明らかになっている。   In addition, the smaller the dispensed amount, the lower the precision of the gravimetric method that undergoes the evaporation phenomenon (the diameter of one bubble is larger), and the limitations of the gravimetric method are revealed.

本発明はピペッタ等の分注器具の検定に利用できる。   The present invention can be used for verification of a dispensing instrument such as a pipetter.

1……分注器具検定装置、2……検定装置本体、3……検定対象分注器具、3A……検出液、10……筐体、11……吸光度検出容器、11A……基準液、11B……分注口、12……検定容器設定溝、13……光源手段、14……フィルタ手段、14A……ブランク光フィルタ、14B……検出光フィルタ、15……光電変換手段、21……フィルタ切換器、21A……回転機構、25……CPU、27……表示手段、35……入力手段、36……制御手段。   DESCRIPTION OF SYMBOLS 1 ... Dispensing instrument test | inspection apparatus, 2 ... Test | inspection apparatus main body, 3 ... Test target dispensing instrument, 3A ... Detection liquid, 10 ... Housing, 11 ... Absorbance detection container, 11A ... Reference | standard liquid, 11B: Dispensing port, 12 ... Calibration container setting groove, 13 ... Light source means, 14 ... Filter means, 14A ... Blank light filter, 14B ... Detection light filter, 15 ... Photoelectric conversion means, 21 ... ... Filter switcher, 21A ... Rotating mechanism, 25 ... CPU, 27 ... Display means, 35 ... Input means, 36 ... Control means.

Claims (2)

試料液体を吸引して所定の分注量の分注液を取り分ける分注器具の検定方法において、
準の波長の光を吸光する第1の吸光度特性を有する第1の色素成分を含む基準液を既知の液量だけ入れた状態において吸光度検出容器に白色光源光を透過させた透過光を受光する光電変換手段から第1の吸光度検出出力を得
上記分注器具によって上記分注液として吸引されかつ上記基準の波長とは異なる波長の光を吸光する第2の吸光度特性を有する第2の色素成分を含む検出液を上記吸光度検出容器に注入して混合液を作った状態において、上記白色光源光を上記基準の波長とは異なる波長の光成分を透過させる検出光フィルタを透過させて当該透過光を上記吸光度検出容器の上記検出液を注入した上記混合液を透過させることにより上記光電変換手段から第2の吸光度検出出力を得、
検定値演算手段によって、上記第1の吸光度検出出力と上記第2の吸光度検出出力との比を求め、上記基準液の上記既知の液量と、上記第1及び第2の吸光度検出出力の比とに基づいて上記検出液の液量を上記分注量の検定値として計算することにより、上記分注器具から上記吸光度検出容器に上記検出液を注入してから上記混合液の吸光度を検出するまでの間の蒸発現象により上記第1及び第2色素成分が減少しないことを利用して、上記分注器具の上記分注量の検定値を求める
ことを特徴とする分注器具の検定方法。
In the verification method of the dispensing instrument that aspirates the sample liquid and separates the dispensing liquid of the predetermined dispensing volume,
Receiving the transmitted light is transmitted through the white light source light absorbance detection container in a state where the reference solution was placed only known liquid volume containing a first dye component having a first absorbance characteristics of absorption of light of a wavelength of standards Obtaining a first absorbance detection output from the photoelectric conversion means ,
A detection liquid containing a second dye component having a second absorbance characteristic that is sucked as the dispensing liquid by the dispensing device and absorbs light having a wavelength different from the reference wavelength is injected into the absorbance detection container. Te in the state mixture was Tsu created, injecting the detection solution with the detection light filter for transmitting transmits light components the transmitted light the absorbance detection cell of a wavelength different from that of the reference of the above white light source light The second absorbance detection output is obtained from the photoelectric conversion means by transmitting the mixed liquid,
A ratio between the first absorbance detection output and the second absorbance detection output is obtained by a test value calculation means, and the ratio between the known liquid amount of the reference solution and the first and second absorbance detection outputs. Based on the above, the liquid volume of the detection liquid is calculated as a test value for the dispensing volume, so that the absorbance of the mixed liquid is detected after the detection liquid is injected from the dispensing device into the absorbance detection container. by utilizing the fact that the first and second color component is not reduced by evaporation phenomena until, assay method of the dispensing instrument and obtains the test value of the dispensing amount of the dispensing device .
試料液体を吸引して所定の分注量の分注液を取り分ける分注器具の検定装置において、
白色光源光を射出する光源手段と、
準の波長の光を吸光する第1の吸光度特性を有する第1の色素成分を含む基準液が入った状態において、上記分注器具によって上記分注液として吸引されかつ上記基準の波長とは異なる波長の光を吸光する第2の吸光度特性を有する第2の色素成分を含む検出液を注入させて混合液を作る吸光度検出容器と、
上記吸光度検出容器に上記基準液が入った状態において上記光源手段から射出される白色光源光を当該吸光度検出容器に透過させ、その後上記吸光度検出容器に上記混合液を作った状態において上記光源手段から射出される白色光源光を上記基準の波長とは異なる波長の光成分を透過させる検出光フィルタを通して当該吸光度検出容器に透過させるフィルタ手段と、
上記吸光度検出容器の透過光を受光して、当該吸光度検出容器に上記基準液が入っている状態において第1の吸光度検出出力を得、かつ当該吸光度検出容器に上記混合液が入っている状態において第2の吸光度検出出力を得る光電変換手段と、
上記基準液の上記既知の液量と上記第1の吸光度検出出力及び第2の吸光度検出出力の比とに基づいて上記検出液の液量を上記分注量の検定値として計算することにより、上記分注器具から上記吸光度検出容器に上記検出液を注入してから上記混合液の吸光度を検出するまでの間の蒸発現象により上記第1及び第2色素成分が減少しないことを利用して、上記分注器具の上記分注量の検定値を求める検定値演算手段と
を具えることを特徴とする分注器具の検定装置。
In the verification device of the dispensing instrument that aspirates the sample liquid and separates the dispensing liquid of the predetermined dispensing volume,
Light source means for emitting white light source light;
In a state where the reference solution containing containing a first dye component having a first absorbance characteristics of absorption of light of a wavelength of standards, the wavelength of the aspirated and the reference as the dispensing liquid by the dispensing device and the absorbance detection container to make a second absorbance detection solution containing a second pigment component having a characteristic by entering Note mixture absorbs light of different wavelengths,
White light source light emitted from the light source means is transmitted through the absorbance detection container in a state where the reference liquid is contained in the absorbance detection container, and then the liquid mixture is formed in the absorbance detection container from the light source means. Filter means for transmitting the emitted white light source light to the absorbance detection container through a detection light filter that transmits a light component having a wavelength different from the reference wavelength;
In the state in which the light transmitted through the absorbance detection container is received, the first absorbance detection output is obtained in the state where the reference liquid is contained in the absorbance detection container, and the mixed solution is contained in the absorbance detection container. Photoelectric conversion means for obtaining a second absorbance detection output;
By calculating the liquid volume of the detection liquid as the assay value of the dispensed volume based on the known liquid volume of the reference liquid and the ratio of the first absorbance detection output and the second absorbance detection output , by utilizing the fact that the first and second color component is not reduced by evaporation phenomenon during the period from the injection of the detection liquid in the photometric detection container from the dispensing device to the detection of the absorbance of the mixed solution And a test value calculation means for obtaining a test value of the dispensed amount of the dispenser.
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