JP2010266349A - Performance inspection container for quantitative titration apparatus, and measuring environment determination method using the container - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a container storing titration liquid, capable of reducing maximally evaporation of the liquid to be titrated from a pipette, and transferring the whole liquid in the pipette, when inspecting titration performance of the pipette. <P>SOLUTION: A chip Pt of a pipette P is inserted from an opening 6a of a main lid 6 of a container 1 having an opened sub-lid 7, and placed on a mass measuring device, and progressed, while piercing a hydrophobic film 5 and a hydrophilic film 4, to thereby titrate the liquid in the pipette into the container. In this case, since a water-holding material 3 is filled into a container body 2, remaining liquid in the pipette is also transferred to the water-holding material 3 side by a capillary phenomenon, and the whole liquid in the pipette is stored into the container 2. The weight of the liquid titrated into the container body in this state is measured, and the volume of the titrated liquid is calculated from the measurement result, to thereby determine the titration performance of the pipette. <P>COPYRIGHT: (C)2011,JPO&amp;INPIT

Description

  The present invention is a container used for accurately measuring the volume of liquid discharged from a liquid quantitative titration device called a pipette or dispenser as a device for quantitatively discharging liquid and measuring the titration performance of these liquid quantitative titration instruments. And the method of determining the suitability of the measurement environment including the performance of the container.

  In order to accurately measure the volume of liquid, a device for titrating a predetermined amount of liquid tends to increase the number of uses as the purpose of use diversifies. In the following, pipettes will be described as representative examples of these devices. With the expansion of the pharmaceutical industry and bio-related market, the worldwide sales volume is around 1.2 million units / year, and the amount will continue to increase in the future. It is expected.

  On the other hand, higher performance is required for pipettes and dispensers due to technological sophistication and the need to guarantee the performance is increasing. For this reason, about 400,000 pipettes are currently inspected and calibrated to maintain their performance, and the number of pipettes is expected to increase further in the future.

However, as the need for inspection and calibration is increasing, a method for inspecting the titration volume in a quantitative titration instrument such as a pipette or a dispenser has not yet been established. Especially for precision pipettes with a volume of 200 μL or less, the inspection is technically difficult. At present, the gravimetric method that measures the mass of the titrated liquid and calculates the volume of the titrated liquid from this measurement result is promising. Several methods have been implemented that are attracting attention as effective inspection means. The following patent documents are inventions relating to this weight method.
US Pat. No. 6,455,787 B1

  Although the gravimetric method is considered to be a promising inspection method in the future, there are still problems to be solved. Hereinafter, a pipette will be described as an example including the examples.

Usually, the gravimetric method is carried out by storing titrated pure water in a container and measuring the mass of the titrated pure water.
Here, the container in which pure water is dripped consists of a container main body that contains pure water and a lid that seals the container main body after titration of pure water, but the entire amount of pure water in the pipette is transferred into the container as described later. The evaporation of pure water during the titration work becomes a problem. For this reason, in order to solve the problem that pure water evaporates, the following methods are adopted, but these methods cause new problems.

[Problems in setting the environment for inspection]
In the performance inspection of a quantitative titration instrument such as a pipette, pure water is usually used as the liquid used as described above. Pure water has low contamination to equipment related to inspections including pipettes, is easily available, the equipment is easy to dry and does not require special consideration for disposal, and has a large heat capacity and is liquid There is an advantage that it is thermally stable and, therefore, the amount of evaporation is small.

  However, since pure water evaporates as a matter of course, when measuring the mass of pure water titrated from a pipette, the evaporation of pure water is suppressed as much as possible, or the amount of evaporation is measured to correct the measured mass value. It is necessary to take some kind of countermeasures for evaporation.

  As a method of suppressing evaporation as much as possible, a method of humidifying the entire indoor space where measurement is performed is conceivable. This method can be realized by making the entire room 50% to 80% stable and high humidity, but it is not very comfortable as an environment for the operator, and the cost of maintaining this high humidity environment for a long time is ignored. It will be impossible. In addition, inconveniences such as failure and performance degradation due to generation of germs, condensation of equipment used, etc. are also expected.

  Further, for example, a mass measuring device required for measuring a very small amount of 20 μL or less requires a minimum scale of 0.001 mg, that is, a performance of about 1 / 1,000,000 g, due to heat generated by a human body such as an operator. There is a high possibility of being sensitive to evaporation fluctuations, and the above-described method of humidifying the room cannot effectively ensure the appropriateness of this inspection.

  In view of the above points, a method has been proposed in which a cover is formed in a measurement space such as the circumference of a weighing pan of a weight measuring device that measures the mass of pure water, and evaporation is suppressed by maintaining a constant humidity in the cover. ing. This method can greatly reduce the space to be kept at high humidity compared with the above method, and the humidity control is easy and economical. However, this method is particularly effective when testing a high performance pipette. Has the same problem as the method.

[Problems such as operability and operation time during inspection]
After setting the environment as described above, for example, in a pipette, a container for receiving a liquid to be titrated is placed on a measuring unit of a weight measuring device such as an electromagnetic balance type electronic balance, and the pipette is operated to operate the pipette. A test medium such as pure water sucked in advance in the tip portion (hereinafter referred to as “chip portion” including the embodiment) is dropped into the container.

  The mass of the dropped liquid (pure water) is measured by the weight measuring device, and the volume of the dropped liquid is calculated using the fact that volume × density = mass, and the performance of the pipette is calculated based on the calculation result. Inspect.

  In the above performance test, there is a problem when the liquid sucked by the pipette at the time of titration is discharged from the tip portion of the pipette, or there is a problem such as the presence of an error factor usually called a Z factor in determining the density of the liquid. . In particular, when discharging the liquid from the pipette, it is necessary to rub the tip of the tip against the inner surface of the container and transfer the entire amount of the remaining liquid in the tip to the container side. The titration amount is slightly different depending on the degree of this, and is the largest error factor when measuring the performance of the pipette including the evaporation of pure water during the operation time.

  More specifically, the tip portion is configured as a consumable item that can be exchanged to prevent the growth of fungi and adhesion of contaminants, and is referred to as polypropylene (hereinafter referred to as “PP”) or polyethylene (hereinafter referred to as “PE”). ).

  Although PP and PE are not extremely hydrophilic or hydrophobic materials, there is a problem that water droplets remain subtly. As a method for solving this problem, the tip of the tip is placed against a container that discharges liquid as described above. A method of removing liquid from the chip by rubbing is encouraged.

  However, recently, the titer has reached a level of 1 μL (1 μg), and it is necessary to use a mass meter capable of measuring an extremely small amount such as a so-called microbalance used for elemental analysis in the gravimetric method. Since the “rubbing” operation itself becomes a disturbance factor for the mass meter and there are individual differences in the operation, this operation causes a measurement error of the mass meter.

  The present invention is configured in view of the above-described problems, and is a container that contains a titrated liquid, and requires and minimizes the environment setting when measuring the weight of the titrated liquid in a pipette performance test. The present invention also relates to a method for determining the suitability of a titration work environment including the performance of the container from the configuration of the container excellent in operability and the measurement data of the weight measuring device.

  That is, the first configuration of the present invention relates to a container that contains the titration liquid, and the configuration of the container main body is filled with a water retention material inside the container main body, and a hydrophilic film is spread on the upper surface of the filler, If necessary, it has a structure in which a hydrophobic film is further spread on the upper part of the hydrophilic film, and if necessary, this container body is attached with a main lid having an opening through which a pipette tip can be inserted, And it is a test | inspection container of the quantitative titration apparatus to which the child lid which seals opening of this parent lid was attached.

  In the second configuration of the present invention, the weight of the test container filled with a liquid such as pure water is continuously measured for a predetermined time, and the change in the measured value is equal to or less than a predetermined threshold value. It is an inspection environment determination system that determines that the use of the container is possible and determines that the environment is inappropriate for the measurement of the mass of the titration liquid, including the performance of the container, if the threshold is exceeded. It is characterized by.

  Since the container is filled with a water retaining material such as a hydrophilic porous material, the liquid in the tip of a quantitative titration instrument such as a pipette easily and almost completely moves to this water retaining material side due to capillary action. The work such as “rubbing”, which is necessary and has individual differences, is unnecessary, and the weight of the discharged liquid can be accurately measured, whereby the liquid discharge amount (volume) can be accurately measured.

  Further, if a hydrophobic film is spread on the surface of the container, it is possible to accurately measure the liquid discharge amount without using a device that moisturizes the weight measurement space.

  In addition, if a container lid is formed on the container and a child cover is formed on the container, the child cover is opened, the tip portion is inserted into a narrow opening through which the tip portion of the pipette can be inserted, and the film inside the container body is broken through. By inserting the tip part into the container body, there is almost no gap between the tip part and the container at the time of titration, so that the evaporation of the liquid at the time of titration can be kept to a minimum. It can be performed accurately in a wide range of environments.

  In addition, since the container is filled with a water retention material, when the tip is inserted into the container body, even if there is liquid remaining in the tip during titration, the remaining liquid moves to the water retention material due to capillary action. The entire amount in the tip portion can be transferred into the container in a short time. Moreover, special skills such as “rubbing” of the conventional method are not required for this total amount transfer.

  Further, according to the second configuration of the present invention, it is possible to determine the suitability of the environment in which the titration operation is performed, including the suitability of using the pipette cuvette.

Embodiments of the present invention will be described below with reference to the drawings.
FIG. 1 shows the configuration of a pipette performance test container showing the first configuration of the present invention.
In FIG. 2A, an arrow 1 indicates a pipette performance inspection container. Reference numeral 2 denotes a main body of a pipette inspection container, and any material such as plastic, glass, metal, etc. is usable, but a transparent material capable of confirming the infiltration state of the titrated liquid is suitable. Further, the shape may be any shape such as a cylindrical shape or a prismatic shape.

3 is a water retaining material filled in the container body 2. As a water retaining material, use a material that releases water as little as possible once it absorbs water. For example, the composition and configuration of a chemically synthesized substance such as a copolymer such as sodium polyacrylate, a starch-based natural material such as corn starch, and a porous material are not limited.
In addition, it is possible to use the water retaining material 3 to which a predetermined amount of liquid has been added in advance, in addition to using a completely dry state.

  The water retaining material 3 need not be limited to one type. For example, the water retaining material 3 may be composed of, for example, a mixture of materials such as a main function of moisture absorption, a main function of moisture retention, and a main function of preventing evaporation. It may be a composite material or a laminate of these materials.

  In addition, if the humidity management of the measurement environment is strictly set and an environment in which the discharge liquid does not evaporate is set, the tip of the pipette is inserted into the container filled with the water retaining material 3 to thereby remove the liquid in the tip. A small amount of liquid remaining at the time of titration also moves to the water retaining material side by capillary action, and the discharge amount can be accurately measured.

  Reference numeral 4 denotes a hydrophilic film stretched to seal the water retaining material 3 on the upper end surface of the water retaining material 3. As the hydrophilic film, for example, polyvinyl alcohol (PVA), polyvinyl formal (PVF) and the like are suitable. The hydrophilic film 4 sucks the liquid in the tip portion when the tip portion of the pipette breaks or pulls out the hydrophilic film 4 as will be described later, and the entire amount of the liquid in the tip portion is transferred into the container body 2. To help.

  Reference numeral 5 denotes a hydrophobic film stretched on the hydrophilic film 4. As the hydrophobic film, for example, tetrafluoroethylene / polytetrafluoroethylene (PTFE), polyvinylidene fluoride / polyvinylidene fluoride (PVDF), and the like are suitable. By spreading the hydrophobic film 5 on top of the hydrophilic film 4, the penetration of moisture from the outside of the container or the diffusion (evaporation) of moisture from the inside of the container is prevented.

  Reference numeral 6 denotes a main lid provided at the upper end of the container body 2, which is configured to be fitted or screwed to the container body 2, and is configured to be detachable from the container body 2 as necessary. Yes. Reference numeral 6a denotes an opening formed in the main lid 6, and the opening area is made small enough to be necessary and sufficient for inserting the tip portion Pt of the pipette P.

  A child lid 7 is attached to the main lid 6 and is a lid for opening and closing the opening 6 a of the main lid 6. In the illustrated configuration, the child lid 7 is configured to be opened and closed with a hinge structure, but it is possible to have a configuration separated from the main lid 6. However, when the structure is separated, a connection type with the main cover 6 as shown in the drawing is desirable in consideration of the possibility of the child cover 7 being lost and the operability.

In the container having the above configuration, titration for pipette performance inspection is performed according to the following procedure.
First, the child lid 7 is opened to open the opening 6a. In this state, the tip portion Pt of the pipette P is inserted into the opening 6a. By this operation, the tip part Pt reaches the water retaining material 3 in the container body 2 through the hydrophobic film 5 and the hydrophilic film 4, and titration is performed in this state.

In the titration, first, since the area of the opening 6a is small and there is almost no gap between the surface hydrophobic film 5 and the hydrophilic film 4 and the tip portion Pt, the liquid such as pure water that has been titrated is There is almost no evaporation outside the container. Further, the liquid remaining in the tip portion Pt during the titration operation is also sucked to the water retaining material 3 side by the capillary action of the water retaining material 3, and the entire amount of the liquid in the tip portion Pt moves to the container side in a short time.
Immediately after the titration is completed, measure the mass of the titrated liquid and inspect the performance of the pipette. Of course, the same method can be used for the dispenser.

FIG. 1B shows a modification of the above embodiment.
Reference numeral 8 denotes a frame, which is configured to be fitted to the upper edge of the container body 2 as shown in the figure. A surface hydrophilic film 4 and a hydrophobic film 5 are stretched on the inner surface of the frame 8 and the upper part thereof, and the films 4 and 5 and the frame 8 as a whole constitute a film unit.

  Since the frame 8 is configured to be detachable from the container body 2, for example, even if a hole is formed in each of the films 4 and 5 by the tip portion Pt of the pipette, a new film can be easily replaced by replacing with a new film unit. Can be replaced. Further, the dried water retaining material 3 can be impregnated with water in advance, or the amount of water impregnated into the water retaining material 3 can be adjusted without breaking the film.

FIG. 2 shows a state in which the performance of the pipette is inspected using the container according to the present invention in a pipette calibration apparatus (Japanese Patent Application No. 2008-172360) proposed separately by the present inventors.
Reference numeral 50 denotes a mass measuring device such as an electromagnetic balance type electronic balance. The load measuring unit centering on the weighing pan 51 of the device 50 is covered with a humidity holding container 52 and stored in a water reservoir of the humidity holding container 52. Further, the inside of the humidity holding container 52 is configured to maintain an appropriate humidity as the water W evaporates.

  The pipette inspection container 1 of the present application is placed with the child lid 7 opened on the holder 53 provided on the weighing pan 51 of the above apparatus, and the pipette P is placed in the container from the opening 52a of the humidity holding container 52. The tip portion Pt of the pipette P is inserted into the pipette P1 through the opening 6a of the pipette inspection container 1 and the surface hydrophobic film 5 and the surface hydrophilic film 4 are inserted into the water retaining material 3 of the container 1 for titration. The titration mass is measured by the mass measuring device 50, and the volume of the liquid is calculated from the measured mass of the titration liquid and displayed on the display unit 54, or used in the second configuration of the present invention to be described later. Is displayed on the screen DS. The necessity of calibration of the pipette P is determined from the calculated value of the volume of the titrated liquid, and the pipette P is calibrated if necessary.

  If this pipetting calibration apparatus is used, the effects of evaporation countermeasures in the apparatus and the effects of evaporation countermeasures of the pipette inspection container 1 according to the present invention can be exhibited in a superimposed manner, so that the volume of the titrated liquid can be calculated most accurately and accurately. Even if this pipette calibration device is not used, if it is not an inappropriate environment such as an extremely dry atmosphere, the normal weighing without the humidification means by the high evaporation prevention means of the pipette inspection container 1 of the present application. It can be measured indoors. In particular, if the container main body 1 is provided with the parent and child lids 6 and 7, it is extremely short to open the child lid 7 for the titration, so that inspection can be performed in a wide range of environments.

FIG. 3 shows a method for determining the performance or inspection environment of the cuvette 1, which is another configuration according to the present invention.
As a method, there are a method of determining in the original process of calibrating the pipette P by measuring the mass of the liquid titrated from the pipette P, and a method of determining separately from the titration from the pipette.

First, a determination method when performing mass measurement for titration from a pipette will be described.
First, the pipette performance inspection container 1 shown in FIG. 1 is arranged on the measuring unit of the mass measuring apparatus (S1), and a predetermined liquid such as pure water is titrated from the pipette P to the container 1 (S2). .

  The mass measuring device continuously measures the mass of the titrated liquid for a predetermined time T after the titration, and measures the change (increase / decrease) in the measured value (S3). In other words, if the value continuously measured during this predetermined time changes to a preset value or more, the amount of evaporation of the titrated liquid is greater than a specified amount, or conversely, the absorption of moisture in an overhumid environment Means that the measurement environment is ineligible.

  Specifically, it is determined whether or not the change in measured mass for a predetermined time (T) is not more than a preset maximum value side threshold value W1 / T and not less than a minimum value side threshold value W2 / T ( S4). In the case of evaporation, the measured value naturally decreases, but on the contrary, the measured value may increase due to moisture absorption from the outside, so the maximum value side threshold W1 / T in the increasing direction and the minimum value side in the decreasing direction It is necessary to set both threshold values of the threshold value W2 / T.

  In step S4, when ΔW / T <W1 / T and ΔW / T> W2 / T, the measurement of the mass of the titration liquid is continued (S5), and the volume of the titration liquid is calculated from the measurement result. (S6), and the result is displayed (S7).

  On the other hand, if either one of ΔW / T <W1 / T and ΔW / T> W2 / T is not established in step S4, the continuation of the titration liquid measurement process is stopped (S8), and the measurement is inappropriate. (S9).

  Subsequently, in step 10, the humidity around the container 1 is measured to determine whether or not the measured humidity M exceeds an allowable value. Here, the allowable value is not the humidity (for example, humidity 50% to 80%) necessary for humidifying the entire room described in the section of the prior art, but the measured humidity M is, for example, A% (for example, 10%) or less. Or, it means an extremely dry state or a wet state such as B% (for example, humidity 90%) or more.

  If the measured humidity is within the allowable value in step 10, it is determined that there is a problem on the side of the container 1 because the measurement environment is appropriate, and “replace container” is displayed (S11). Conversely, if M> B% or M <A%, the measurement environment is inferior and an instruction is given to adjust the humidity (S12).

  The above method is a determination method performed in the step of measuring the mass of the titration liquid as a pre-stage of the calibration of the pipette P. In addition to the determination method, the measurement environment or the performance of the container 1 itself is determined. This method can also be implemented.

  That is, a predetermined amount of liquid is dropped on the container 1 (S13), this container is placed on the mass measuring device (S1), and the performance or measurement environment of the container 1 is determined by executing the above-described steps S3 and S4. . If it is determined from the determination result that there is no problem in the performance of the container 1 or the measurement environment, the steps S3 and S4 can be omitted in the subsequent titration and mass measurement processes of the pipette to be inspected. It becomes.

  FIG. 2 shows a state in which the present invention is implemented using a high-functional apparatus capable of appropriately maintaining humidity. However, a container having a configuration unique to the present invention is used, and the performance of the container or the measurement environment is measured. If the determination method is carried out, measurement can be performed even when the weighing unit centering on the weighing pan of the weight measuring device is opened to the atmosphere.

(A) is sectional drawing of the pipette test container which concerns on the Example of the 1st structure of this invention, (B) is a cross-sectional partial view of the pipette test container which shows the modification of the structure shown to (A). It is a figure which shows an example of the use condition of the pipette test container which concerns on this invention using a mass measuring device. It is a flowchart which shows the determination method of the measurement environment using the pipette test container which is the 2nd structure of this invention.

1 Container for testing quantitative titration equipment (Pipette testing container)
DESCRIPTION OF SYMBOLS 2 Container main body 3 Water retention material 4 Hydrophilic film 5 Hydrophobic film 6 Parent lid 6a (parent lid) opening 7 Child lid 8 Frame 50 Mass measuring device 51 Weighing pan 52 Humidity holding container 53 Holder 54 Display part

Claims (8)

A container used for measuring the mass of a titration liquid by containing a liquid titrated from a quantitative titration instrument such as a pipette or a dispenser. The container absorbs or holds the titrated liquid or absorbs the liquid. One or more kinds of water retention materials as materials for preventing evaporation of the liquid are filled, and the liquid titrated from the quantitative titration device is configured to be absorbed by the water retention material. . 2. A container for performance test of a quantitative titration instrument according to claim 1, wherein a hydrophilic film is stretched over the surface of the water retaining material filled in the container body so as to cover the water retaining material. 3. A container for performance test of a quantitative titration instrument according to claim 2, wherein a hydrophobic film is stretched on top of the hydrophilic film in the container body. A frame body that is detachably engaged with the upper edge of the container body is formed, and a film unit is formed on the frame body by spreading at least one of a hydrophilic film or a hydrophobic film. 4. The container for performance inspection of a quantitative titration instrument according to claim 2, wherein the container can be opened without damaging the container. 2. A container for performance inspection of a quantitative titration instrument according to claim 1, wherein the water retaining material in the container body is infiltrated with a liquid in advance. A first step of installing the performance test container of the quantitative titration instrument in the weight measuring device, a second step of titrating the liquid into the performance test container of the quantitative titration instrument, and a measured value of the mass of the titrated liquid A third step for measuring a change in the predetermined time, a fourth step for determining whether or not the amount of change in the measured value is within a preset threshold value, and pipette performance inspection based on the determination result A measurement environment determination method using a container for performance inspection of a quantitative titration instrument, comprising: a fifth step of determining the performance of the container and determining the quality of the measurement environment. A first step of filling the performance test container of the quantitative titration apparatus with liquid, a second step of installing the performance test container of the quantitative titration apparatus filled with liquid in the weight measuring device, and the mass of the filled liquid A third step for measuring a change in the measured value for a certain period of time, a fourth step for determining whether or not the amount of change in the measured value is within a preset threshold, and a determination based on the determination result A measurement environment determination method using a performance test container for a quantitative titration instrument, comprising: a fifth step of determining the performance of the performance test container for the titration instrument and determining the quality of the measurement environment. A sixth step of measuring the humidity of the measurement environment when the measurement environment is determined to be inappropriate in the fifth step, and the humidity measured in the sixth step is a preset upper limit value of humidity and 7. It is determined that the performance of the container for performance measurement of the quantitative titration instrument is poor when it is within the lower limit, and it is judged that the measurement environment is poor when it is other than the upper limit and lower limit of the preset humidity. 8. A measurement environment determination method using the container for performance inspection of the quantitative titration instrument according to 7.

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