WO2019229872A1

WO2019229872A1 - Leak detection device and leak detection method

Info

Publication number: WO2019229872A1
Application number: PCT/JP2018/020722
Authority: WO
Inventors: 雄介近; ステファンシュランクラー; アジャイクマールシン
Original assignee: 旭化成メディカル株式会社
Priority date: 2018-05-30
Filing date: 2018-05-30
Publication date: 2019-12-05

Abstract

An aspect of the present application comprises a leak detection device (1) for detecting leaks from a filtration membrane M, the device being provided with: a container (10) that is separated into two spaces due to the filtration membrane M being disposed therein; a liquid storage container (20) for storing liquid to be supplied to the container (10); a first connection pipe (30) for connecting the liquid storage container (20) with either one of the spaces inside the container (10); a gas supply device (40) for supplying a gas to the container (10); a second connection pipe (50) for connecting the gas supply device (40) to the container (10); closing means (61, 62, 63) provided in the first connection pipe (30) and/or the second connection pipe (50); and a detection member (70) for detecting leaking of the gas supplied by the gas supply device (40) from the filtration membrane M.

Description

Leak detection device and leak detection method

The present invention relates to a leak detection apparatus and a leak detection method. More specifically, the present invention relates to an apparatus and a method for detecting a leak of a filtration membrane that can detect micro defects such as pinholes existing in the filtration membrane with high sensitivity.

Membrane separation using a filtration membrane is used in many fields as a simple and low-consumption material separation method. Such membrane separation is basically based on the principle of sieving a substance to be subjected to filtration according to the size of the pores present in the membrane. Therefore, it is important for the performance of the membrane that the pores of a desired size are uniform.

On the other hand, defects may occur in the filtration membrane during the manufacturing process and use of the filtration membrane. The most typical one is a defect called a pinhole, which is a relatively large hole with respect to the original hole of the filtration membrane. If there is a pinhole, the substance passing through the pinhole is not subjected to the sieving action, so that the substance to be excluded is mixed into the filtered substance and the separation efficiency is lowered.

As a method of detecting pinholes that are minute defects in the filtration membrane, one space partitioned by the filtration membrane is pressurized with gas and the other is filled with liquid. A method using the surface tension of a liquid is known in which the presence or absence of a pinhole is examined by applying a pressure that flows out from the hole and measuring the flow rate of the gas leaking from the pinhole portion.

For example, Patent Document 1 (Japanese Patent Laid-Open No. 1-307409) discloses a method for directly measuring the gas flow rate on the supply side (raw solution side) after a certain time after the start of pressurization, the gas on the hollow fiber side (filtrate side), Three measurement methods are shown: a method for measuring the flow rate of the liquid extruded by the above method, or a method for measuring a decrease in the liquid level on the hollow fiber side (filtrate side) (see Patent Document 1).

Patent Document 2 (Japanese Patent Laid-Open No. 60-94105) describes a method for measuring a pressure change due to gas leakage by a pressure drop on the stock solution side or a gas leak (corresponding to the amount of gas supplied). Two measurement methods, that is, a direct measurement method using a gas flow meter attached to the side, are shown (see Patent Document 2).

Further, Patent Document 3 (Japanese Patent Application Laid-Open No. 5-157654) discloses a method in which an airtight gas chamber is provided on the filtrate side and the gas leakage is measured by the pressure increase on the leaked side (Patent Document 3). reference).

However, if the number of pinholes is small or the number is small, the amount of gas that leaks is small, so the conventional method of directly measuring the gas flow rate measures the slight gas flow rate with a direct instrument with high accuracy. It was difficult to do.

In addition, the method of measuring the amount of liquid extruded with gas and the method of reading a pressure change by providing a gas chamber on the liquid enclosure side can indirectly measure a slight gas flow rate with high accuracy. When the pressurized membrane expands significantly or when precise measurement is required that cannot ignore the expansion of the membrane, the outflow or pressure of the gas due to the outflow of liquid or pressure change due to the expansion of the membrane Since it occurs simultaneously with the change and usually cannot be distinguished, there is a problem that the measurement accuracy is lowered.

In order to solve this problem, conventionally, one of the spaces partitioned by the membrane is pressurized with a gas such that the gas does not flow out of a normal hole, and the other space is filled with a liquid. By measuring the flow rate of the gas leaking from the pinhole of the membrane, by measuring the flow rate of the liquid pushed out by the gas, or by providing a gas chamber on the liquid enclosure side and reading the pressure change, pinhole etc. Attempts have been made to improve the apparatus and detection method for detecting a leak of a filtration membrane due to a defect of the filter, that is, to solve the problem that the expansion of the filtration membrane due to pressurization reduces the measurement accuracy (for example, (See Patent Document 4).

Japanese Patent Laid-Open No. 1-307409 JP-A-60-94105 JP-A-5-157654 Japanese Patent No. 3502912

However, when actually performing a filtration treatment of a solution using a sterilized filtration membrane, the user removes the cap from the liquid passage port of the filtration membrane module (a container with a nozzle or a port containing the filtration membrane) Since the tube of the liquid processing circuit is connected to the liquid passage port, the sterilization state of the filtration membrane module (aseptic state, that is, the state where the internal and external partition walls are not opened after sterilization processing) is impaired. There was a fear. Leak detection is performed before the use of the filtration membrane, but according to conventional leak detection technology, when performing a leak test on a filtration membrane used under aseptic conditions for virus removal or the like, the filtration membrane is removed. In some cases, the separation membrane device (also referred to as “filtering device” or “filtration system” in this specification) is taken out from the sterilized state and destroyed.

Therefore, in view of the difficulty in maintaining sterility with conventional leak detection technology, the present invention can accurately and efficiently detect leaks, and can detect leaks in filtration membranes used in aseptic conditions. It is an object of the present invention to provide a leak detection device and a leak detection method that can be carried out under aseptic conditions.

In order to solve such a problem, one aspect of the present invention is a leak detection device that detects a leak of a filtration membrane,
A container that is separated into two spaces by having a filtration membrane installed therein;
A liquid storage container for storing the liquid supplied to the container;
A first connecting pipe connecting the liquid storage container and one space in the container;
A gas supply device for supplying gas to the container;
A second connection pipe connecting the gas supply device and the container;
Closing means provided on the first connecting pipe and / or the second connecting pipe;
A detection member for detecting leakage from the filtration membrane of the gas supplied by the gas supply device;
It is an apparatus provided with.

According to such a leak detection device, a filtration membrane to be detected is installed in a container, and gas is supplied to one of the spaces (regions) separated by the filtration membrane. At this time, from one region of the filtration membrane, If it is detected that gas leaks to the other region, it can be determined that a leak has occurred.

In addition, this leak detection apparatus including a container in which a filtration membrane is installed, a liquid supply apparatus that supplies liquid to the container, and the like is configured to constitute a filtration apparatus or a filtration system. In other words, since the leak test of the filtration membrane can be performed in the filtration device or the filtration system, the leak test is not performed by taking out the virus removal membrane alone and destroying the aseptic condition, but performing the filtration device or filtration. It can be carried out aseptically without removing it from the system.

The leak detection device of the above aspect may further include a control member that controls the gas supply device, the detection member, and the closing means.

In the leak detection device of the above aspect, the detection member may include a pressure detector.

In the leak detection device of the above aspect, the detection member may be a differential pressure gauge.

In the leak detection device of the above aspect, the detection member may include an air chamber.

The leak detection device of the above aspect may include a means for keeping the volume in the air chamber constant.

In the leak detection device of the above aspect, the detection member may be a flow meter.

In the leak detection apparatus of the above aspect, the detection member may be configured with a member that can be subjected to stationary sterilization and / or stationary cleaning.

In the leak detection device of the above aspect, the filtration membrane may be a virus removal membrane.

In the leak detection device of the above aspect, the filtration membrane module including the filtration membrane and the container may include an aseptic connection member.

In the leak detection device of the above aspect, the filtration membrane may be a hollow fiber membrane.

A leak detection method according to an aspect of the present invention is a leak detection method of a filtration membrane using the leak detection device of the above aspect,
A filling step of filling a secondary chamber with a liquid in a container having two spaces separated by a filtration membrane;
One of the spaces is pressurized with a gas supplied from a gas supply device, and a detection step of detecting leakage of the gas from the filtration membrane is included.

In the leak detection method of the above aspect, the filling step may be performed by supplying a liquid from a liquid storage container.

The leak detection method of the above aspect may include a discharge step of discharging the liquid filled in one space after the filling step.

The leak detection method of the above aspect may be automatically controlled by a control unit provided in the leak detection apparatus.

INDUSTRIAL APPLICABILITY According to the present invention, a leak detection apparatus and a leak detection method that can detect leaks accurately and efficiently, and can perform leak detection of filtration membranes used in aseptic conditions under aseptic conditions. Can be provided.

It is a figure which shows the outline of a leak detection apparatus. It is a figure which shows the circuit structural example of a leak detection apparatus. It is a figure explaining the process of filling the secondary side of a filtration apparatus with water. It is a figure explaining a pressurization (stabilization time) process. It is a figure explaining the process which pressurizes (measures) and detects gas leakage. It is a figure explaining the membrane separation operation | work implemented as it is as it is using the filtration membrane determined to be defect-free (pass) after a leak test implementation. It is a flowchart which shows an example of a leak test. It is a graph which shows the relationship between the diameter of the pinhole of a filter in Example 1, and the pressure rise value at the time of performing the leak test of the said filter. In Example 2, it is a graph which shows the relationship between the diameter of the pinhole of a filter, and the leakage flow rate of the gas at the time of performing the leak test of the said filter.

A preferred embodiment of the present invention will be described with reference to the accompanying drawings.

The leak detection device is a device that performs a leak test of a filtration membrane and detects whether or not a defect such as a pinhole has occurred in the filtration membrane. The leak test here refers to, for example, a test in which the filtration membrane is pressurized from the inside while the filtration membrane is wetted with a liquid to check whether gas leaks from the membrane (see FIG. 1).

When, for example, a hollow fiber membrane is used as a filtration membrane, the hollow fiber membrane is attached to the inside of the housing (container) 10, and the hollow fiber membrane is pressurized with gas in a state where the inside of the housing 10 is filled with a liquid. Measure the coming gas visually or with a sensor. In the case of visual observation, it is determined whether or not open bubbles are generated. In the case of a sensor, a method of measuring the flow rate of pressurized gas on the pressurized side across the hollow fiber membrane, or leakage to the liquid filling side. A method of measuring a change in pressure due to air can be used (see FIG. 1). In addition, the types of gas leaking from the filtration membrane include jets from leaked parts (defects such as pinholes) (visible) and diffuse flows from normal parts without defects (not visible) There are two types.

FIG. 2 shows the leak detection apparatus according to the first embodiment. The leak detection device 1 of the present embodiment includes a housing 10, a liquid storage container 20, a liquid supply pipe 30, a gas compression apparatus 40, a gas supply pipe 50, a drain pipe 55, a liquid collection pipe 58, a pump 61, valves 62 to 66, A filtration device (separation device) that includes a pressure detector 70, a control unit 80, etc., and performs virus removal or the like using a filtration membrane, and in the separation device, the filtration membrane is removed from the device. The apparatus is configured as a device capable of performing a leak test without being taken out.

The housing 10 is a container that is separated into two spaces or regions by installing the filtration membrane M therein. For example, when a cylindrical hollow fiber membrane is used as the filtration membrane M as in this embodiment, the interior of the housing 10 is divided into two spaces, a columnar region inside the hollow fiber membrane and a cylindrical region outside the hollow fiber membrane.

In the present specification, when the filtration membrane M is used as a virus removal filter in a filtration device, the state or region before filtration is referred to as primary (side), and the state or region after filtration is referred to as secondary (side). . In the case of this embodiment in which fluid flows from the inside to the outside of the hollow fiber membrane during filtration, the columnar region inside the hollow fiber membrane is the primary side (primary chamber) and the cylindrical region outside the inside of the housing 10. Is the secondary side (secondary chamber). Needless to say, if the flow of the fluid during filtration is reversed, the primary and secondary are interchanged.

The housing 10 of this embodiment includes a cylindrical body 14 having a circular cross section and a pair of headers 15 attached to each of the open ends (see FIG. 1 and the like). The headers 15 (15a, 15b) are provided at both ends of the body portion 14 of the housing 10, respectively. Each header 15 (15a, 15b) is formed with

nozzles

16a, 16b serving as fluid inlets and outlets (see FIG. 1).

Ports

17 a and 17 b are formed on the side of the body 14 of the housing 10.

In addition, in FIG. 1, the center axis | shaft of the housing 10 which is a cylindrical container is shown with the code | symbol P. FIG. The direction along the central axis P is the longitudinal direction of the housing (tubular container). Further, the direction around the central axis P is the circumferential direction (circulation direction). The housing 10 of the present embodiment is installed with the central axis P being vertical (see FIG. 2 and the like). Of course, this is merely an example, and the orientation is not particularly limited.

The liquid storage container 20 is a container in which a liquid (for example, protein solution) supplied to the housing 10 is stored. The liquid storage container referred to in this specification can include not only a container that does not deform regardless of the liquid storage amount, but also a container that deforms according to the liquid storage amount (for example, a bag-like material such as a plastic bag).

The liquid storage container 20 and the housing 10 are connected to each other by a liquid supply pipe (first connection pipe) 30 formed of, for example, a tube. The liquid in the liquid storage container 20 is supplied through the liquid supply pipe 30 to one space in the housing 10 partitioned by the hollow fiber membrane M. On a supply system including the liquid supply pipe 30, for example, the liquid supply pipe 30, a liquid feeding pump 61 and a valve (closing means) 62 for opening and closing the liquid supply pipe 30 are provided.

The gas compression apparatus (for example, an apparatus including an air compressor or a gas cylinder) 40 functions as a gas supply apparatus that supplies gas to the housing 10. The gas compression device 40 of the present embodiment pressurizes air and supplies the air into the housing 10 through a gas supply pipe (second connecting pipe) 50.

The gas supply pipe 50 is constituted by a tube, for example, and connects the gas compression device 40 and the housing 10. The air sent out from the gas compression device 40 is adjusted to a pressure that does not flow out from a normal hole by a pressure regulator (not shown), and is partitioned by the hollow fiber membrane M in the container 10 through the gas supply pipe 50. Is supplied to the other space. The gas supply pipe 50 is provided with a sterilization film 52 and a valve 63. The sterilization film 52 includes a filter that removes bacteria from the supplied air. The valve 63 is a valve (closing means) for opening and closing the gas supply pipe 50. For example, an air regulator is used as the pressure regulator.

The liquid collection pipe 58 is a pipe used when collecting the filtered liquid, and one end side is connected to the port 17b of the housing 10 and the other end side is connected to a liquid collection container (not shown). A valve 66 is provided in the middle of the liquid collection pipe 58.

The pressure detector 70 is a device that functions as a detection member that detects whether or not the gas (air) supplied from the gas compression device 40 leaks from the hollow fiber membrane M. As the pressure detector 70, Series 35X HT (Keller) can be suitably used. In the leak detection device 1 of the present embodiment, an air chamber (gas chamber) 72 is provided in the exhaust pipe 55 connected to one port 17a of the housing 10, and a valve 64 is provided upstream and a valve is provided downstream. 65 is provided (see FIG. 2 and the like). The pressure detector 70 detects a pressure change (pressure increase) in the air chamber 72 under the condition that the valve 64 is opened and the valve 65 is closed. The pressure detector 70 may be a measuring instrument that can detect a change in the internal pressure of the air chamber 72, and a differential pressure gauge can also be used. Further, it is not necessary to provide the air chamber 72 separately. In that case, the volume in the exhaust pipe 55 is kept constant by closing the valve 65, and the pressure detector 70 directly connected to the exhaust pipe 55 is used. What is necessary is just to detect the pressure change in the exhaust pipe 55.

The air chamber 72 may be provided with means for keeping the volume in the air chamber 72 constant. Although detailed illustration is omitted, the flow of liquid (for example, water) generated due to the expansion of the filtration membrane M and the accompanying pressure increase in the liquid filling portion when the gas is pressurized with the gas compression device 40 during the leak test Are preferably removed using such means. Specifically, for example, the valve 65 is opened, the flow accompanying the expansion of the filtration membrane M is discharged to remove the pressure rise, and the space up to the valve 65 is automatically filled with liquid, thereby sealing gas. Such a means can be configured by a mechanism that keeps the volume of the space constant. According to this means, a minute leak can be accurately detected.

The control unit 80 performs operation control of pumps, valves, etc., and reception of signals such as detection results of the pressure detector 70. The control unit 80 according to the present embodiment is connected to the pump 61, the valve 62, the valve 63, the valve 64, the valve 65, the valve 66, and the pressure detector 70, and operates these or displays information on the detected pressure. Receive (see FIG. 2). Although not shown in detail, the control unit 80 stores a computer that transmits an operation signal to each device or receives a detection signal, a program for causing the computer to execute a leak test execution procedure, and the like. Consists of memory, etc. The leak test can be performed under automatic control by using an automatic control program for automatically performing the leak test.

The procedure for performing the leak test of the hollow fiber membrane M in the leak detection apparatus 1 having the above-described configuration will be described with an example (see FIGS. 3 to 7).

[Filter membrane setup]
The filtration membrane M or the filtration membrane module is attached to the separation membrane device (filtration device or filtration system). The filtration membrane M or the filtration membrane module is sterilized in advance by steam sterilization or the like and is in a sterilized state. However, when attaching to the separation membrane device, the sterility may be impaired by opening the connection part. After the filtration membrane M or the filtration membrane module is attached to the separation membrane device, stationary sterilization (SIP) and / or stationary cleaning (CIP) is performed to sterilize the inside of the separation membrane device (filtration device or filtration system). Is possible. In said embodiment, it is preferable that the detection member is comprised with the member in which stationary sterilization (SIP) and / or stationary cleaning (CIP) are possible. For example, a member made of stainless steel or fluororesin can be used, but is not limited thereto.

Further, the filtration membrane module can be installed in a separation membrane device (a filtration device or a filtration system) sterilized in advance with an aseptic connection member such as an aseptic connector. In this case, after the filtration membrane module is attached, aseptic conditions can be maintained without performing stationary sterilization (SIP) and / or stationary cleaning (CIP).

[Secondary water filling]
The secondary side (secondary chamber) of the filtration device is filled with liquid (water) (step SP1). Specifically, with the valve 63 of the gas supply pipe 50 and the valve 66 of the liquid collection pipe 58 closed, the valve 62 of the liquid supply pipe 30 and the

valves

64 and 65 of the discharge pipe 55 are opened, and the pump 61 is driven to supply the liquid in the liquid storage container 20 (in this embodiment, water) (see FIG. 3). The liquid is supplied to the primary side of the housing 10 through the nozzle 16b, passes through the filtration membrane M, is supplied to the secondary side (secondary chamber), and is further discharged to the outside through the discharge pipe 55 from the port 17a.

In addition, in such a filling process (step SP1), it is implemented for the purpose of filling the secondary side (secondary chamber) with liquid (water). However, in the leak detection apparatus 1 configured as in the present embodiment, When the liquid is supplied and filled from the liquid storage container 20 due to the structure of the apparatus, both the primary side (primary chamber) and the secondary side (secondary chamber) are filled with liquid (water). (See FIG. 3).

[Pressurization (stabilization)]
When the filling of the liquid (water) into the secondary chamber is completed (Yes in step SP2), the primary space is pressurized with gas (step SP3). Specifically, the valve 62 of the liquid supply pipe 30 is closed, the valve 63 of the gas supply pipe 50 is opened, and the gas compressing device 40 is driven to supply gas (in this embodiment, air) (FIG. 4). reference). The gas is supplied to the primary side of the housing 10 through the nozzle 16a. The primary side is kept pressurized with gas until the system is stabilized (stabilization time), and then the valve 65 of the exhaust pipe 55 is closed and the process proceeds to the measurement step (step SP4).

In addition, although detailed description here is abbreviate | omitted, after the liquid filling process, before moving to a pressurization (stabilization) process, the liquid with which one space (primary side, primary chamber) was filled is discharged | emitted. It is good also as shifting to the following pressurization (stabilization) process after implementing a discharge process.

[Pressure (Measurement)]
It is detected whether or not the gas supplied to the primary side has leaked from the filtration membrane M (step SP4). When leaking, gas leaks from the port 17 and the internal pressure of the air chamber 72 changes (increases), and the pressure detector 70 senses the amount of change in this pressure. Usually, even normal filtration membranes without defects such as pinholes, the measured values are not zero due to gas diffusion, etc., so the average and standard deviation (σ) of these values are measured, and preset standards If a value exceeding the value is detected, it is determined that gas leakage has occurred (Yes in step SP4), and it is determined that the filtration membrane M is defective (step SP5). In addition, as a reference value at this time, for example, a value of average + 3σ or higher, a value of average + 4σ or higher, a value of average + 5σ or higher, a value of average + 6σ or higher, or the like can be used as a determination reference. On the other hand, when the pressure change value is small, it is determined that no gas leaks from the defective portion (No in step SP4), and it is determined that the filtration membrane M has no defect (pass) (step SP6).

When the leak test is performed as described above and it is determined that there is no defect (pass) in the filtration membrane M (step SP6), in the leak detection device of the present embodiment, the filtration membrane M determined as having no defect is used as it is. A membrane separation operation can be performed (see FIG. 6). That is, after the liquid in the liquid storage container 20 is replaced with a liquid to be filtered (in the case of the present embodiment, a protein solution) (the replacement with the protein solution is performed by directly replacing the solution in the liquid storage container 20 with the protein solution). Or may be performed by preparing a plurality of liquid storage containers in parallel and switching and flowing the solution line according to the steps), and the valve 63 and the exhaust pipe of the gas supply pipe 50 The

valves

64 and 65 of 55 are closed, the valve 62 of the supply pipe 30 and the valve 66 of the liquid collection pipe 58 are opened, and the pump 61 is driven to supply the liquid in the liquid storage container 20. The liquid is supplied to the primary side of the housing 10 through the nozzle 16b, passes through the filtration membrane M determined to have no defect (passed), is supplied to the secondary side (secondary chamber), and is separated from the membrane. Liquid is fed from the port 17b through the liquid collection tube 58 to a liquid collection container (not shown) (see FIG. 6).

As described above, according to the leak detection apparatus 1 of the present embodiment as described above, the filtration membrane M that is the target of leak detection is installed in the circuit of the separation membrane apparatus (filtration apparatus or filtration system) (in the housing 10) ( In the set-up state, gas is supplied to one of the spaces (regions) separated by the filtration membrane M. At this time, it is detected that gas leaks from one region of the filtration membrane M to the other region. If so, it can be determined that a leak has occurred.

Further, in this leak detection apparatus 1, it is possible to perform liquid filtration (membrane separation) of a solution (protein solution or the like) using the filtration membrane M after the leak test as it is. Therefore, since it is not necessary to destroy the aseptic state of the filtration membrane M that is the subject of filtration by the leak test, it is possible to perform a series of steps of performing filtration through the leak test while maintaining the aseptic state. is there. In other words, the present embodiment including a container (housing 10) in which the filtration membrane M is installed, a liquid supply device (liquid supply pipe 30, pump 61) for supplying liquid to the container (housing 10), and the like. Since the leak detection device 1 of the embodiment has a structure that can constitute a separation membrane device (filtration device or filtration system) as it is, the leakage test of the filtration membrane M is performed in the separation membrane device (filtration device or filtration system). Realized. For this reason, the leak test is not carried out by taking out the virus removal membrane alone and destroying the aseptic condition, but performing it while maintaining the aseptic condition without removing it from the separation membrane device (filtration device or filtration system). Can do.

Although this embodiment can be applied to any filtration membrane M, the filtration membrane M includes a virus removal membrane having particularly high virus removal performance and high protein permeation performance. With regard to the virus removal film, detection of pinholes with high accuracy is desired because of the required high removal capability. According to the leak detection apparatus 1 as in the present embodiment, such high accuracy detection is simple and efficient. Can be realized. As the virus removal membrane, a membrane made of regenerated cellulose, PVDF, PES, or the like can be used. Moreover, the form of the virus removal membrane may be a flat membrane or a hollow fiber membrane.

The above-described embodiment is an example of a preferred embodiment of the present invention, but is not limited thereto, and various modifications can be made without departing from the gist of the present invention. For example, in the above-described embodiment, the configuration in which the pump 61 that functions as the liquid feeding unit and the valve 63 that functions as the closing unit is provided in the liquid supply system, but this is only a preferable example. When the liquid supply pipe 30 can be closed by the pump 61, the pump 61 can be configured to function as a closing means without using the valve 62.

In the above embodiment, an example in which a cylindrical hollow fiber membrane is used as the filtration membrane M has been shown, but this is also only a suitable example. For example, a flat membrane-like filtration membrane may be employed other than the hollow fiber membrane. Although not specifically described here, the primary chamber 11, the secondary chamber 12 (see FIG. 1), the body portion 14, the header 15, the nozzle 16, the port 17, and the like of the housing 10 are appropriately set according to the filtration membrane M. sell.

In the above-described embodiment, as an example of the housing 10, a container that is separated into two spaces or regions by installing the filtration membrane M therein is illustrated, but when separated into “two” here, Includes literally two spaces, as well as the case of “two” spaces when physically separated by three or more.

In the above embodiment, the case where the pressure detector 70 is used as a device for detecting the presence or absence of gas leakage from the filtration membrane M has been described (see FIG. 5), but this is also only a preferred example. . For example, as a member for detecting gas leakage, a fluid detection device can be used in addition to such a pressure detection device. An example is as follows. That is, when the gas supplied to the primary side leaks from the filtration membrane M, the fluid flow is also generated inside the gas supply pipe 50. Therefore, although a detailed description is omitted, a flow meter (see reference numeral 70 ′ in FIGS. 1 and 5) that detects the flow of the fluid is employed instead of the pressure detector, and the flow of the fluid in the gas supply pipe 50 and the like is determined. By sensing, it is possible to detect gas leakage from the filtration membrane M.

In the above-described embodiment, the form in which the liquid in the liquid storage container 20 is supplied into the housing 10 has been described, but this is also only a suitable example. In addition, for example, although detailed illustration is omitted, the filtration membrane module (a module including the housing 10 and the filtration membrane M provided in the housing 10) in a state in which a liquid is filled in advance ( It is also possible to carry out a leak test by immediately pressurizing after being placed in a separation membrane device (filtration device or filtration system) with a sterile connecting member such as a sterile connector.

The aseptic connector (indicated by reference numeral 90 in FIG. 1) is not shown in detail, but for example, a tubular insertion portion to be inserted into the connection tube, a flange-like connection portion, a connection surface provided on the connection surface, and the pipeline is sealed. A sealing tape is provided. The aseptic connector 90 includes a male type and a female type, and a combination of a pair of identical shapes. For example, the connection surface of one sterile connector 90 and the connection surface of the other sterile connector 90 are fitted together. And the like, such that the sealing tape interposed between the connecting surfaces is pulled out and the tubes are connected to each other while maintaining the sterility (for example, Japanese Patent No. 6285961) ,reference). By attaching the sterile connector to the filtration membrane M in advance, it can be connected to a pipe or the like while maintaining the sterile condition.

Using the leak detection apparatus 1 having the configuration described in the above embodiment, nine filters (hollow fiber membranes M) having pinholes and seven filters (hollow fiber membranes M) having no pinholes are targeted for leak detection. A leak test was performed. The measured filter is “Planova” manufactured by Asahi Kasei Medical Corporation. “BioEX” (registered trademark) having a membrane area of 1 m ² was used. As the filter having a pinhole, a hollow fiber membrane M in which a pinhole having a size of 4.4 to 7.7 μm was formed using a krypton fluoride (KrF) excimer laser was employed.

As a measurement procedure, first, a filter is attached to the leak detection device 1, then the pump 61 is operated to send water from the liquid storage container 20 to the housing 10, and further, the filter (hollow fiber membrane M) is passed through the housing 10. The inside was filled with water. Thereafter, water filled in the primary side of the filter is discharged from a drain nozzle (not shown) provided between the pump 61 and the header 16 on the liquid supply pipe 30 disposed, for example, downward in the housing 10. After that, the valve 62 and the valve 63 are operated to drive the gas compressing device 40 (an air cylinder may be used instead of driving the gas compressing device 40) to send compressed air to the housing 10 and pressurize the filter. did. In addition, the sterility at the time of drainage was ensured by providing a sterilization filter in said drainage nozzle.

The measurement conditions were a pressure of 343 kPa and a stabilization time of 300 seconds. During the pressurization of the filter within the stabilization time, the test liquid pushed out by the expansion or gas of the filter passes through the air chamber 72 (volume: 29 mL) provided outside the housing 10 and is on the side of the air chamber 72. The state in which the

valves

64 and 65 of the exhaust pipe 55 were opened so as to flow out of the system from the exhaust pipe provided on the side (see Table 1).

[Example 1]
The amount of leak was measured using a pressure detector (differential pressure gauge) 70 connected to the air chamber 72. After the stabilization time, the valve 65 was closed, and the pressure increase value after 30 seconds was read. The results are shown in FIG. A filter with a pinhole showed a higher pressure rise value than a filter without a pinhole, and the larger the pinhole diameter, the higher the pressure rise value. It can be seen from FIG. 8 that the presence or absence of a pinhole can be easily determined from the magnitude of the pressure increase value.

[Example 2]
A flow meter 70 ′ was installed in the gas supply pipe 50 connecting the gas compression device 40 (an air cylinder may be used) and the housing 10 (see FIGS. 1 and 5), and the amount of leakage was measured. The

valves

64 and 65 were kept open even after the stabilization time had elapsed, and the volume flow rate value for 60 seconds was read. The results are shown in FIG. A filter with a pinhole showed a higher volumetric flow rate value than a filter without a pinhole, and the larger the pinhole diameter, the higher the volumetric flow rate value. From FIG. 9, it can be seen that the presence or absence of pinholes can be easily determined from the magnitude of the leakage flow rate value.

The present invention is suitable for application to a leak detection device and a leak detection method for detecting a leak of a filtration membrane.

DESCRIPTION OF SYMBOLS 1 ... Leak detection apparatus, 10 ... Housing (container), 11 ... Primary chamber (one space), 12 ... Secondary chamber (the other space), 14 ... trunk | drum, 15 (15a, 15b) ... Header, 16 ( 16a, 16b) ... Nozzle, 17 (17a, 17b) ... Port, 20 ... Liquid storage container, 30 ... Liquid supply pipe (first connecting pipe), 40 ... Gas compression device (gas supply device), 50 ... Gas supply Pipe (second connecting pipe), 52 ... sanitizing membrane, 55 ... draining pipe, 58 ... collecting pipe, 61 ... pump (closing means), 62 ... valve (closing means), 63 ... valve (closing means), 64... Valve, 65... Valve (means for keeping the volume in the air chamber constant), 66... Valve, 70... Pressure detector (detection member), 70 ′. ... Control part, 90 ... Aseptic connector (sterile connection member) , M ... Hollow fiber membrane (filtration membrane)

Claims

A leak detection device for detecting a leak of a filtration membrane,
A container that is separated into two spaces by installing the filtration membrane inside;
A liquid storage container for storing the liquid supplied to the container;
A first connecting pipe connecting the liquid storage container and one space in the container;
A gas supply device for supplying gas to the container;
A second connecting pipe connecting the gas supply device and the container;
Closing means provided on the first connecting pipe and / or the second connecting pipe;
A detection member for detecting leakage of the gas supplied by the gas supply device from the filtration membrane;
A leak detection apparatus comprising:
The leak detection device according to claim 1, further comprising a control member that controls the gas supply device, the detection member, and the closing means.
The leak detection device according to claim 1 or 2, wherein the detection member includes a pressure detector.
The leak detection device according to claim 1 or 2, wherein the detection member is a differential pressure gauge.
The leak detection device according to any one of claims 1 to 4, wherein the detection member includes an air chamber.
The leak detection apparatus according to claim 5, further comprising means for keeping a volume in the air chamber constant.
The leak detection device according to claim 1 or 2, wherein the detection member is a flow meter.
The leak detection device according to any one of claims 1 to 7, wherein the detection member is a member capable of stationary sterilization (SIP) and / or stationary cleaning (CIP).
The leak detection device according to any one of claims 1 to 8, wherein the filtration membrane is a virus removal membrane.
The leak detection device according to any one of claims 1 to 9, wherein a filtration membrane module including the filtration membrane and the container includes an aseptic connection member.
The leak detection device according to any one of claims 1 to 10, wherein the filtration membrane is a hollow fiber membrane.
A leak detection method for a filtration membrane using the leak detection device according to any one of claims 1 to 11,
A filling step of filling a secondary chamber with a liquid in the container having two spaces separated by the filtration membrane;
A detection step of pressurizing the one space with a gas supplied from the gas supply device and detecting leakage of the gas from the filtration membrane.
The filtration membrane leak detection method according to claim 12, wherein the filling step performs filling by supplying a liquid from the liquid storage container.
The method for detecting a leak of a filtration membrane according to claim 12 or 13, further comprising a discharge step of discharging the liquid filled in the one space after the filling step.
The filtration membrane leak detection method according to any one of claims 12 to 14, wherein the leak detection device is automatically controlled by a control unit provided in the leak detection device.