JPH03205533A - Storage container for calibration liquid for gas sensor and gas partial pressure adjusting method - Google Patents

Abstract

PURPOSE:To enable accurate calibration by providing a 1st container where the calibration liquid for the sensor is charged and a 2nd gas-impermeable container wherein the 1st container is sealed, and setting the transmissivity values of the 1st container to CO2 and O2 above specific values. CONSTITUTION:The 1st container 2 where the calibration liquid for the sensor is charged and the 2nd gas-permeable container 3 where the 1st container 2 is sealed are provided and the gas partial pressure in liquid to be inspected is measured. The CO2 and O2 transmissivity values of the 1st container 2 need to be >=0.1ml/m<2>.day.atm (at 20 deg.C) and are, preferably, >=10ml/m<2>.day.atm (at 20 deg.C). The gas partial pressure can be accurately adjusted by the storage container for the calibration liquid for the gas sensor and the gas partial pressure adjusting method and held constant, so the accurate calibration is enabled.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a storage container for a gas sensor calibration solution, which is suitably used for calibration of various gas sensors, and a gas partial pressure adjustment method.

Conventional technology> Gas sensors are used in many fields to measure gas partial pressure during the night of the test, and in the medical field, blood is sampled from an extracorporeal blood circulation circuit and its C.
Measurement of O2 partial pressure, O2 partial pressure, etc. is being carried out.

In particular, in recent years, an extracorporeal circulation monitoring device has been developed that incorporates a gas sensor into the extracorporeal blood circulation circuit and is capable of continuously measuring the partial pressure of gases in the blood in real time. -286381).

When using such a gas sensor, CO2
Calibration (initial scale setting) is performed using a gas sensor calibration liquid (hereinafter also simply referred to as calibration liquid) whose partial pressure and 02 partial pressure are known.

In this case, it is necessary that the gas partial pressure of the calibration solution does not change over time during storage, so the calibration solution is packed and stored in a tightly packed state in a substantially gas-impermeable flexible container ( (U.S. Pat. No. 4,116,336, etc.).

However, although the above container is filled with a calibration liquid that has been adjusted to a predetermined gas partial pressure,
When the container is sealed, the gas partial pressure of the calibration liquid tends to change, which causes a problem in calibration errors.

In addition, in the above-mentioned extracorporeal circulation monitoring device, since the calibration solution passes through a part of the blood circulation circuit, it is necessary to store the calibration solution in a sterile state.The container filled with the calibration solution must be sterilized, especially by high-pressure steam sterilization. (autoclave sterilization) may be considered.

However, when a so-called aluminum laminate bag, in which an aluminum sheet and a resin film are laminated and integrated, is used as a gas-impermeable container, when the bag is sterilized using high-pressure steam, the gas in the laminated resin film is removed by high temperature and high pressure. Due to the rapid increase in permeability, gas permeation increases at the heat-sealed part of the container, and especially for gases with low solubility such as 02 gas, the gas partial pressure changes significantly before and after sterilization. A disadvantage is that it is impossible to maintain the gas partial pressure after sterilization.

As described above, conventional storage containers have the disadvantage that the gas partial pressure of the calibration liquid changes during filling with the calibration liquid and further during sterilization, resulting in errors in calibration.

<Problems to be Solved by the Invention> The present invention has been made in view of the above-mentioned drawbacks of the prior art, and its purpose is to accurately adjust the gas partial pressure and maintain the set gas partial pressure constant. An object of the present invention is to provide a storage container for a gas sensor calibration solution and a gas partial pressure adjustment method.

Means for Solving the Problems> Such objects are achieved by the present invention as described in (1) to (5) below.

(1) A first container filled with a gas sensor calibration solution;
A storage container for a calibration solution for a gas sensor, comprising a second container that is substantially gas-impermeable and encloses the first container.

(2) The CO2 and 02 permeability of the first container are each 0. 1 ml/m"day-atm (at2 0℃
) The storage container for the gas sensor calibration solution according to (1) above.

(3) A gas sensor calibration solution is filled and sealed in a first container having gas permeability, and then the first container is placed in a predetermined gas atmosphere to adjust the gas partial pressure of the gas sensor calibration solution. Further, the first container is sealed in a second substantially gas-impermeable container to prevent the gas of the gas sensor calibration liquid from being contained. A method for adjusting gas partial pressure of a gas sensor calibration liquid, characterized by maintaining the pressure constant.

(4) Fill the first container with gas permeability with the gas sensor calibration solution and seal it, then perform high-pressure steam sterilization on the first container, and then place the first container in a predetermined gas atmosphere. to adjust the gas partial pressure of the gas sensor calibration solution, and further encapsulating the first container in a substantially gas-impermeable second container to maintain the gas partial pressure of the gas sensor calibration solution constant. A method for adjusting gas partial pressure of a calibration liquid for a gas sensor, characterized in that:

(5) The CO■ and 02 permeability of the first container are each 0. 1 mj/m2dayatm (at2 0℃
) The method for adjusting the gas partial pressure of a gas sensor calibration liquid according to (3) or (4) above.

<Example> Hereinafter, preferred embodiments of the gas sensor calibration liquid storage container and gas partial pressure adjustment method of the present invention will be described in detail with reference to the accompanying drawings.

FIG. 1 shows a storage container (
A front view showing a configuration example of a storage container (hereinafter also simply referred to as a storage container),
FIG. 2 is a sectional view taken along the line n-11 in FIG. 1.

As shown in these figures, the storage container 1 of the present invention has a structure in which a first container 2 filled with a calibration agent 4 and sealed is enclosed in a second container 3.

Both the first container 2 and the second container 3 are made by folding a flexible sheet material in half and sealing the three sides by, for example, heat fusion, ultrasonic fusion, or high frequency fusion. It is made into a bag shape.

The first container 2 has a certain degree of gas permeability, and the permeability of CO2 and 02 is O and 1 mj/, respectively.
m2-day-atm (at 20℃) or higher, especially 10 mj/m"day-atm (
at. 20°C) or higher, and more preferably 100 mj/m”day-atm, respectively.
(at 20°C) or higher.

Transparency is 0. 1 mj/m2dayatm (a
If the temperature is less than t 2 0° C.), it will take time to adjust the gas partial pressure of the calibration liquid filled in the first container 2, and the practicality will be poor.

Examples of the constituent material of the first container 2 that can provide such gas permeability include polyvinyl chloride, polyester, polyethylene, polypropylene, ethylene-vinyl acetate copolymer, or a laminate of two or more of these.
Among these, soft polyvinyl chloride is particularly preferred in terms of heat resistance, ease of fusing, flexibility, and workability.

In this case, the degree of polymerization of the flexible polyvinyl chloride is 500 to 5.
000 is preferable.

In addition, as a plasticizer for this flexible polyvinyl chloride, for example, di(ethylhexyl) phthalate (DEHP)
．． Di(n-decyl) phthalate (DnDP) etc. are used, and other DOA. DOS. DOM, citric acid ester (A.THC), etc. may also be used.

The content of such a plasticizer is preferably about 10 to 100 parts by weight based on 100 parts by weight of polyvinyl chloride.

Furthermore, a stabilizer or the like may be added to the sheet material of the first container 2. Examples of the stabilizer include epoxy compounds and Ca-Zn stabilizers.

The thickness of the sheet material of the first container 2 is usually about 0.01 to 2 mm, particularly about 0.01 to 2 mm, although it depends on its constituent materials.
It is preferable to set it as about 1-1 mm.

Further, the width of the seal portion 21 of the first container 2 is preferably about 2 to 20 mm in consideration of prevention of peeling during heat treatment, especially high-pressure steam sterilization, and ease of handling.

The first container 2 is filled with a calibration liquid 4 having a known gas partial pressure of one or more gases to be measured by the gas sensor.

In the medical field, when gas partial pressure in blood is measured, C 2 O 2 partial pressure and O 2 partial pressure are mainly measured, so these will be used as a representative example below.

When calibrating such a gas sensor for measuring blood gas partial pressure, calibration liquids having two or more different gas partial pressures are used.

For example, CO2 partial pressure = 80 mmHg. Calibrated iMA with 0 2 partial pressure = 1 5 0 mmHg and CO2 partial pressure = 40 mmHg. Calibration 7 nights B with 02 partial pressure = 40 mmHg was used, and these calibration solutions A and B were
Each is stored in two storage containers 1.

Note that the gas partial pressure during the calibration period 4 is preferably adjusted by the method described below.

The amount filled into the first container 2 during calibration 4 is not particularly limited, but is between 10 and 1000 ml! It is preferable to set it as approximately.

The second container 3 functions as a packaging material for the first container 2 and is a substantially gas-impermeable container. Here, "substantially gas-impermeable" refers to cases where no gas permeates at all, or cases where gas permeation is extremely small to the extent that there is almost no problem in maintaining the 9 gas partial pressure of the calibration liquid 4. It is a concept that also includes.

As a rough guide, the C O 2 and 02 permeability of the second container 3 are each 0. 1 mj/m2day・atm
(at. 20° C.) or lower, but it is not limited to this as it varies depending on various conditions.

The constituent materials of the second container 3 include polyvinyl chloride, polyethylene, oriented polyethylene, low density polyethylene, polypropylene, nylon, polyacrylonitrile, polymethacrylonitrile, polyvinylidene chloride, polyester, polyethylene terephthalate, etc. Examples include a laminate of two or more of the following.

Alternatively, a laminate of metal foil such as aluminum foil and one or more of the resin sheets described above may be used.

The thickness of the sheet material of the second container 3 should be such that it can achieve the desired gas impermeability or low permeability, and also allow thermal fusion, ultrasonic fusion, high frequency fusion, or adhesion. Although it depends on its constituent materials, it is usually 0.01
It is preferably about 2 mm, particularly about 0.05 to 1 mm.

Further, the width of the seal portion 31 of the second container 3 is preferably about 2 to 100 mm in consideration of preventing gas permeation due to peeling or the like or an increase in gas permeation through the seal portion.

Note that it is preferable that the internal space 32 of the second container 3 be filled with a gas similar to a mixed gas for gas partial pressure adjustment, which will be described later. In other cases, it is preferable to keep the internal space 32 as small as possible.

When taking out the calibration solution from such a storage container 1 and using it, first open the second container 3 and take out the first container 2, then insert a puncture needle or the like into the first container 2 to see inside. Flow out the calibration solution and supply it to the gas sensor. Further, both the first container 2 and the second container 3 may be punctured with a puncture needle or the like.

In addition, in this invention, a 1st container and a 2nd container are not limited to the thing of the said structure.

For example, the first container may be rigid (for example, made of glass,
A gas permeable membrane such as the seed material is installed on a part of the container (for example, the opening of a glass bottle) (for example, the opening of a glass bottle) to obtain the desired gas permeability of the container as a whole. It may be something you have done.

Further, the second container may be a substantially gas-impermeable container made of the same rigid material as described above, and which is airtight when the cap is closed.

Further, in the present invention, in addition to the first container 2 and the second container 3, a third container (not shown) is provided, and the second container is placed in the third container, or the second container is placed in the second container. It is also possible to enclose it in the second container in a state in which it is placed in the third container. The third container may be provided for various purposes, such as adjusting gas permeability and reinforcing the container.

Note that FIGS. 1 and 2 show a state in which the calibration solution 4 is stored in the storage container 1, but in the storage container of the present invention, the first container containing the calibration solution is sealed in the second container. The state may be the previous state or the state before the first container is filled with the calibration liquid.

Next, a method for adjusting the gas partial pressure of the gas sensor calibration liquid of the present invention will be explained.

[Step 1] The first container 2 is filled with a predetermined calibration liquid and sealed.

The first container 2 is sealed by fusing (thermal fusing, ultrasonic fusing, high frequency fusing, etc.) or adhering the three sides (sealing portion 21) of the sealing material folded in half.

Specifically, it is preferable to seal a portion of the seal portion 21 while leaving it unsealed, inject the calibration fluid into the first container 2 from the unsealed portion, and then seal the unsealed portion.

Incidentally, the first container may be formed by stacking two sheets and sealing the four sides of the periphery.

[Step 2] The first container 2 filled with the calibration liquid 4 and sealed is placed in a sterilizer, and the calibration liquid 4 is sterilized with high pressure steam (autoclave sterilization) together with the first container. The sterilization conditions in this case are not particularly limited, and for example, sterilization may be carried out at about 115 to 126°C for about 15 to 30 minutes.

Further, if the calibration liquid 4 does not require sterilization (for example, if it is used in a field other than medical care), this step 2 is omitted.

[Step 3] The first container 2 is placed in a predetermined gas atmosphere, and the gas partial pressure of the calibration liquid 4 is adjusted.

An apparatus for adjusting such gas partial pressure is shown in FIG.

As shown in the figure, a sealed container 6 made of metal, such as stainless steel, is placed in a constant temperature bath 5, and an air pipe 8 from a gas cylinder 7 filled with d mixture gas for gas partial pressure adjustment is sealed. It communicates with the inside of the container 6.

Further, the airtight container 6 is provided with an exhaust pipe 9.

A valve 1 is installed in the middle of the air supply pipe 8 and the exhaust pipe 9, respectively.
0 and 11 are provided.

The valves 10, 1l may be either electromagnetic valves or manually opened/closed valves.

With the first container 2 placed in the airtight container 6, the valve 10
is opened, and the mixed gas in the gas cylinder 7 is introduced into the closed container 6 through the air pipe 8. Also, at this time, the valve 11
is opened, and the air in the closed container 6 is exhausted through the exhaust pipe 9. As a result, the inside of the closed container 6 is replaced with the mixed gas. In this mixed gas, the mixing ratio of CO2 gas and 02 gas is set so as to give a desired gas partial pressure to the calibration port.

The mixed gas in the closed container 6 is at a constant pressure (for example, normal pressure)
and a constant temperature (e.g. room temperature) due to the action of the constant temperature bath 5.
This state is maintained for a predetermined period of time (for example, 1 to 10 days).

Since the first container 2 has gas permeability, the gas partial pressure reaches equilibrium over time, and the calibration liquid in the first container 2 is adjusted to a predetermined gas partial pressure. At this time, if external treatment such as stirring or vibration is applied to the calibration liquid in the first container 2, the time required to reach equilibrium can be further shortened.

Note that during the adjustment of the gas partial pressure, it is preferable to repeatedly introduce and exhaust the mixed gas in the closed container 6 or at regular intervals. Thereby, the gas partial pressure (which changes due to gas exchange with the calibration liquid) within the closed container can be kept constant.

[Step 4] The first container 2 in which the gas partial pressure of the calibration liquid has been adjusted is sealed in the second container 3.

The second container 3 is sealed on three sides of the sheet material folded in half (
This is done by fusing (thermal fusing, ultrasonic fusing, etc.) or adhering the seal portion 31).

In addition, similar to the above, the second container is made by stacking two sheets,
It may be one in which the four peripheral sides are sealed. When the sheet material is a laminate containing the aluminum foil, if the sheet material is sealed on four sides, it is possible to prevent bottle holes from occurring at the folds.

In addition, when sealing the first container 2, it is preferable to seal the mixed gas in the second container.

Since the second container 3 is substantially gas-impermeable, the gas partial pressure of the calibration filter 4 is maintained for a long period of time.

Conventionally, after adjusting the gas partial pressure of the calibration solution, the calibration solution was filled into a gas-impermeable container and then sterilized. The gas partial pressure was changing, making it inaccurate.

On the other hand, in the present invention, the gas partial pressure of the calibration liquid is adjusted after filling and sealing the first container with the calibration liquid and further sterilizing the first container. After adjusting the gas partial pressure of the calibration liquid, the first container is enclosed in a second container that is substantially gas-impermeable, so the gas partial pressure of the calibration liquid remains constant without any change over time. .

<Experiment example> Experimental examples of the present invention will be described below.

(Experimental Example 1) As a calibration solution, 50 mj of an aqueous solution containing the following components was filled into a bag (size: 8 x 9 cm) made of polyvinyl chloride sheet with a sheet thickness of 0.39 mm, and
It was sealed by side heat sealing (sealed portion width: 10 mm).

Note that the gas permeability of this bag (first container) is C O
2 gas and 02 gas are respectively 1 2000 and 1 900 m9/m2dayatm (at.
20°C).

School ball JLA Dan N a 2H P 0 . 2
0. 6mM/jNaH2PO4
20. 6mM/jNaHC
○ 3 10. lmM/j
NaCj2 0
．． 5mM/j for this calibration solution bag at 121°C;
High-pressure steam sterilization was performed for 20 minutes.

Then, use the gas partial pressure adjustment device shown in Figure 3 to calibrate the
A bag containing T& is heated with mixed gas (CO2 = 9.80%,
02:5.09%, N2:85:11%) and left in a closed container maintained at 25° C. and 1 atm. Note that the mixed gas in the airtight container was replaced every hour.

Remove the bag from the airtight container over time and place it in the Radio
Blood gas analyzer manufactured by eter (product name = ABL-3)
C O 2 partial pressure of the calibration solution filled in the bag at 0) (
p co. ) and 02 partial pressure (po2) were measured. The results are shown in the graph of FIG.

? Oh, the horizontal axis of the graph in Figure 4 is the storage time in a sealed container (unit: two days), and the vertical axis is the calibration? Night P Co■ and PO
2 (unit: mmHg), and the number n at each measurement point is 3.

As shown in Figure 4, in this experimental example, the calibration relative PCO
reached equilibrium in 4 days, and P02 in 1 day. At this time, pco2 is 100. 4mmHg, PO2 was 56.2+nmHg.

(Experimental Example 2) The bag containing the calibration liquid whose gas partial pressure was adjusted in Experimental Example 1 was wrapped in a three-layer aluminum laminate sheet (
Aluminum laminate bag (manufactured by Inu Nippon Printing Co., Ltd.)
Size: l2 x 12cm) and heat seal on 3 sides (
It was sealed with a seal portion width of 10 mm). At this time, the inside of the aluminum laminate bag was previously replaced with the mixed gas used in Experimental Example 1.

Table 1? In this aluminum laminate bag, the only part where gas permeation can occur is the polypropylene layer in the heat-sealed part, and taking into consideration the gas permeability of that part and calculating the gas permeability of the aluminum laminate bag as a whole, CO2 gas and 0■ gas are each 0.015
~0.025 and 0.0035~0. O O
7 5 mj/m2-day-atm (at20℃
).

This double-sided calibration solution storage container was left in the atmosphere, and the P CO2 and PO2 of the calibration solution filled in the bag was measured using the blood gas analyzer used in Experimental Example 1. The results are shown in the graph in Figure 5. . Note that the horizontal axis, vertical axis, and number n in this figure are the same as in FIG. 4.

In this experimental example, we followed the change in the calibrated liquid gas partial pressure over time until the 30th day, but PCO■. Both po2 shows good stability. In other words, the variation in gas partial pressure over 30 days is Δ
P.C.O. =-1.4mmHg, ΔP 02= + l
．． O mm}Ig, and it can be said that there is virtually no variation in gas partial pressure.

(Experiment Example 3) As a comparative experiment, p co2 was set to 102.2 mmHg in advance.
．． The same calibration solution as above with P O 2 adjusted to 54.1 mm}Ig was filled into an aluminum laminate bag (size: 8 x 9 cm) similar to that used in Experimental Example 2, and sealed on three sides (sealed part width: 10 mm). ) and then autoclaved at 121° C. for 20 minutes.

After high-pressure steam sterilization, the p co2 and P02 of the calibration solution in the bag were measured.
CO2=-3. 4mmHg, Δpo. =-
1 1. 7 mmHg, and considerable gas partial pressure fluctuations occurred.

Effects of the Invention> As described above, according to the gas sensor calibration solution storage container and gas partial pressure adjustment method of the present invention, it is possible to accurately adjust the gas partial pressure and maintain it constant. This allows for more accurate calibration.

In particular, this effect can be obtained even when the calibration solution is sterilized, which is advantageous in cases where a sterile calibration solution is required, such as in the medical field.

4

[Brief explanation of drawings]

FIG. 1 is a front view showing an example of the configuration of a storage container for a gas sensor calibration solution according to the present invention. FIG. 2 is a sectional view taken along the line ■-■ in FIG. 1. FIG. 3 is a front view schematically showing a configuration example of a gas partial pressure adjusting device used in the gas partial pressure adjusting method of the present invention. FIG. 4 is a graph showing changes over time in gas partial pressure during seven calibration nights during gas partial pressure adjustment in Experimental Example 1 of the present invention. FIG. 5 is a graph showing the change over time in the gas partial pressure of the calibration calculation during storage in Experimental Example 2 of the present invention. Explanation of symbols 1...Storage container 2...First container 3...Second container 2l, 31...Seal portion 32...Inner space 4...Calibration liquid 5...Thermostatic chamber 6 ... Airtight container 7 ... Gas cylinder 8 ... Air pipe 9 ... Exhaust pipe 1 0, 1 1 ... Valve applicant Terumo Corporation agent

Claims (5)

[Claims] (1) A first container filled with a gas sensor calibration solution;
A storage container for a calibration solution for a gas sensor, comprising a second container that is substantially gas-impermeable and encloses the first container. (2) The CO_2 and O_2 permeability of the first container is
Each 0.1ml/m^2・day・atm (at 20℃
) The storage container for a gas sensor calibration solution according to claim 1. (3) A gas sensor calibration solution is filled and sealed in a first container having gas permeability, and then the first container is placed in a predetermined gas atmosphere to adjust the gas partial pressure of the gas sensor calibration solution. Further, the first container is enclosed in a substantially gas-impermeable second container to maintain a constant gas partial pressure of the gas sensor calibration liquid. Partial pressure adjustment method. (4) Fill the first container with gas permeability with the gas sensor calibration solution and seal it, then perform high-pressure steam sterilization on the first container, and then place the first container in a predetermined gas atmosphere. to adjust the gas partial pressure of the gas sensor calibration solution, and further encapsulating the first container in a substantially gas-impermeable second container to maintain the gas partial pressure of the gas sensor calibration solution constant. A method for adjusting gas partial pressure of a calibration liquid for a gas sensor, characterized in that: (5) The CO_2 and O_2 permeability of the first container is
Each 0.1ml/m^2・day・atm (at 20℃
) The method for adjusting the gas partial pressure of a calibration liquid for a gas sensor according to claim 3 or 4.