EP3528934A1 - Method for determining a permeation property of hollow fibre membranes - Google Patents
Method for determining a permeation property of hollow fibre membranesInfo
- Publication number
- EP3528934A1 EP3528934A1 EP17797250.2A EP17797250A EP3528934A1 EP 3528934 A1 EP3528934 A1 EP 3528934A1 EP 17797250 A EP17797250 A EP 17797250A EP 3528934 A1 EP3528934 A1 EP 3528934A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- hollow
- hollow fiber
- fiber membrane
- housing
- liquid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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- 238000000034 method Methods 0.000 title claims abstract description 88
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 20
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- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 claims description 13
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- -1 polyvinylpyrollidone Polymers 0.000 description 5
- 229910052782 aluminium Inorganic materials 0.000 description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 4
- 239000000385 dialysis solution Substances 0.000 description 4
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
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- 230000006872 improvement Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
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- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
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Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
- B01D63/02—Hollow fibre modules
- B01D63/021—Manufacturing thereof
- B01D63/0233—Manufacturing thereof forming the bundle
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/08—Hollow fibre membranes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
- G01N15/0806—Details, e.g. sample holders, mounting samples for testing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
- G01N2015/084—Testing filters
Definitions
- the invention relates to a method for determining a permeation property of hollow fiber membranes.
- the invention relates to a method with which the "clearance”, in particular the "diffusive clearance" of hollow-fiber membranes, can be determined from a determined permeation property.
- the invention relates to an apparatus for carrying out a method for determining the permeation properties of hollow fiber membranes in a hollow fiber membrane bundle, and their use.
- the invention relates to a method for producing hollow fiber membrane bundles of hollow fiber membranes having predetermined permeation properties.
- Hollow fiber membranes are widely used in the purification of liquids.
- hollow fiber membranes are used in medical technology for water treatment and blood purification, especially in the dialysis of kidney patients.
- Corresponding hollow-fiber membranes are installed in hollow-fiber membrane bundles in filter modules. The production of such filter modules for blood purification is now carried out in mass production scale.
- the hollow fiber membranes used for the purification of blood often consist of polysulfone (PSU) and polyvinylpyrrolidone (PVP) and are usually prepared by a so-called dry-wet spinning process.
- PSU polysulfone
- PVP polyvinylpyrrolidone
- a spinning solution containing the polymers PSU and PVP and a solvent is extruded through an annular die into a hollow spun yarn.
- the filament is first guided vertically through an air space, the so-called precipitation gap.
- a coagulation medium is extruded simultaneously with the extrusion to the spun yarn, which starts a coagulation process in the dope of the spun yarn.
- phase inversion occurs, so that so-called sol and gel phases form within the strand.
- the spun yarn is introduced after passing through the precipitating gap in a precipitation bath, in which the thread is completely brought to precipitation and forms the solid hollow fiber membrane structure. Subsequently, the obtained hollow fiber membrane passes through several rinsing baths and drying zones. Depending on the preset spinning conditions, hollow fiber membranes having a different pore structure are obtained.
- PSU is understood in the context of this application as a generic term for all polymers containing sulfonic groups such as polyethersulfone and polyphenylsulfone and copolymers comprising these polymers.
- a plurality of hollow fiber membranes is extruded simultaneously and in parallel in a production plant, so that the obtained after passing through the production plant hollow fiber membrane fibers can be combined as a group of threads or fiber bundles and are taken up by a reel.
- the manufacturing process of hollow fiber membranes is a continuous process that is operated in the production facilities in three-shift operation. It is therefore continually necessary to monitor the quality of the fibers produced in order to avoid larger production errors. Therefore, it is constantly checked if the properties of produced hollow fiber membrane are in the specified range and the production process proceeds according to the preset conditions.
- hollow fiber membranes with different permeation properties for example, so-called “high flux” or “low flux” hollow fiber membranes can be obtained.
- Corresponding hollow-fiber membranes differ in their separation behavior and are therefore suitable, e.g. in the dialysis of kidney patients, for different therapeutic procedures.
- a test method e.g. according to DIN / EN / ISO 8637: 2014.
- the hollow fiber membrane bundles For the construction of filter modules, the hollow fiber membrane bundles must be formed in a filter housing and encapsulated end.
- the casting of the hollow-fiber membrane bundle at the fiber ends takes place with the aid of curable resin compositions, in particular with polyurethane.
- the casting itself and the curing are time-consuming process steps.
- the construction of filter modules and the following analyzes on the filters in the production laboratories can take up to several hours. During this time, the production of hollow fiber membranes continues. If in doubt, it may happen that the analysis results after a few hours show that the specifications of the manufactured hollow fiber membrane are no longer complied with, so that the production result of several hours must be discarded.
- the results of the analysis indicate that the hollow fiber membranes produced meet the specifications, then the corresponding production result of hollow fiber membranes can be further processed into corresponding filter modules.
- kidney filters are used for the blood purification of kidney patients.
- the blood purification of kidney patients is based on the principle of transmembrane mass transfer. It will Blood in along the inner cavity of the hollow-fiber membranes, also called lumen, out, while on the outside of a corresponding dialysis fluid is flowed. The flow direction of the liquids is opposite, so that a filtration using the countercurrent principle.
- undesirable metabolites such as urea, creatinine, ⁇ -2-microglobulin, interleukin-6, phosphate are removed from the blood by permeating them through the membrane wall and being taken up by the dialysis fluid.
- dissolved constituents of the dialysis fluid can also permeate through the membrane wall onto the blood side.
- the dialysis fluid is provided as an aqueous physiological solution containing electrolytes (for example, Na +, K +, Mg 2+, Ca 2+, Cl "), glucose, and a buffer (such as NaHC0 3) included.
- liquid and substances therein permeate through the membrane according to a transmembrane pressure gradient.
- diffusive mass transport the permeation of substances through the membrane occurs due to the molecular intrinsic motion of the solutes and a concentration gradient that exists across the membrane wall.
- the filtration process can be carried out according to one or the other type. If e.g. for the blood treatment in a hemofiltration or hemodiafiltration process, hollow-fiber membranes with relatively large pores are used and / or high flow rates of the two fluid streams, blood and dialysate, are preset, so that part of the filtration is convective.
- the separation of harmful plasma proteins in the blood of kidney patients can only be achieved in therapeutic methods in which a convective mass transfer is possible.
- Such plasma proteins are in the so-called middle molecular weight range.
- Known proteins in the middle molecular range are ⁇ -2 microglobulin and interleukin-6.
- the separation efficiency with which harmful metabolites are removed during the purification of blood by hollow-fiber membranes is referred to as clearance.
- Methods for determining the clearance of hollow fiber membranes are known in the art. For example, the standard DIN / EN / ISO 8637: 2014 describes a standardized method for determining clearance.
- the specification in particular the specification for clearance, in particular the specification of the diffusive clearance of a hollow fiber membrane is important in order to be able to monitor the production process.
- Another object of the invention was to provide a device under the use of hollow fiber membrane bundles can be examined and the diffusive clearance of the hollow fiber membranes can be determined.
- a further object of the invention was also to provide a production process of hollow fiber membranes, which makes it possible to produce hollow fiber membranes within a production process so that before production for the hollow fiber membranes defined range of at least one Permeationseigenschaft, especially the clearance, more particularly the diffusive Clearance, can be met.
- the invention relates to a method for producing hollow fiber membrane filter modules according to claims 15 to 17 using a method according to claims 1 to 12.
- permeation property of a membrane designates the characteristic of a transmembrane mass transfer, which is characterized by a permeation of a substance through a membrane Membrane wall is related.
- a permeation property of a membrane provides information about the pore structure of the membrane and is understood as a measure with which a membrane can be characterized in terms of its porous structure. Permeation observed through the transmembrane mass transfer is generally considered in relation to other quantities.
- the term also means how much of a substance per unit of time can be separated from a liquid by permeation. Based on the initial concentration of the substance, this permeation value indicates the "clearance.” In this sense, the clearance is understood as a permeation property describing the membrane.
- hollow fiber membrane bundles are formed in a housing of a filter module and encapsulated end with a casting resin in the housing by methods of the prior art.
- the end space between the fibers is filled with the casting resin, so that no fluid can penetrate the interspace between the fibers.
- the lumens of the hollow fiber membranes are closed at the ends.
- the lumens of the hollow fiber membranes are exposed again by the end part of the grout is separated.
- the hollow-fiber membranes only have to be closed at the end on one side and placed in a housing in order to be measured.
- the term “molding in” is understood to mean a process in which a hollow-fiber membrane bundle is introduced into a housing
- a hollow-fiber membrane bundle is deformable and can be introduced under compression into the housing so that the bundle is inside the housing is under tension and exerts a force on the inner surface of the housings
- the term “introduction” thus also a process to be understood, in which a compressed hollow fiber membrane bundle is inserted into a housing such that the hollow fiber membrane bundle strives to expand according to its tension, thereby completely filling the inner space of the housing with hollow fiber membranes.
- Hollow fiber membrane bundles form a resistive force in such a packing as a hollow fiber membrane bundle, meaning that a hollow fiber membrane bundle is compressible and builds up a restoring force upon compression Compressed hollow-fiber membrane bundles endeavor to return to a relaxed state
- the restoring force is in particular also associated with a corrugation of the hollow-fiber membranes, which used in the production of hollow fiber membranes.
- Corresponding methods for producing hollow-fiber membranes and hollow-fiber membrane bundles are known from the prior art, for example from DE 100 07 327 A1.
- test liquid is to be understood as meaning a liquid with which a membrane can be examined with regard to a permeation property
- test liquids may be, for example, aqueous solutions or pure water, but in particular also blood plasma or blood
- membrane-like in the context of the present application means that the test liquid, or part of the test liquid, is from the lumen of the hollow-fiber membrane permeate through the membrane wall into the outer environment of the hollow fiber membrane.
- test substance is understood as meaning a substance which is a constituent of a test fluid .
- test substances may represent dissolved constituents of a test fluid, for example salts or water-soluble compounds.
- the method according to the invention for determining at least one permeation property, in particular the clearance of hollow-fiber membranes comprises the following steps:
- Hollow fiber membranes having a first end and a second end, wherein the lumens of the hollow fiber membranes at the first end of the
- Hollow-fiber membrane bundle open at the end, in particular liquid-permeable and at the end of the second end of the hollow-fiber membrane bundle
- Hollow fiber bundle is aligned with the end open lumen of the hollow fiber membranes to the at least one liquid inlet at the first end of the housing
- the method according to the invention comprises the following steps:
- Providing a hollow fiber membrane bundle comprising a plurality of hollow fiber membranes having a first end and a second end, the openings of the lumens of the hollow fiber membranes open at the first end of the hollow fiber membrane bundle, in particular liquid-tight, and end-closed at the second end of the hollow fiber membrane bundle, in particular liquid-tight, are,
- a housing for receiving the hollow-fiber membrane bundle having a first end and a second end, the first end of the housing having at least one liquid inlet and the second end of the housing having at least one liquid outlet,
- Hollow fiber membranes is aligned for at least one liquid inlet and the second end of the hollow fiber membrane bundle is directed with the end closed lumen of the hollow fiber membranes to at least one liquid outlet,
- the method according to the invention has the advantage that the clearance, in particular the diffusive clearance, of the hollow-fiber membranes can be determined quickly and reliably. This has the advantage, in particular in processes for producing hollow-fiber membranes, of being able to promptly control the production process on the basis of the clearance values obtained. As a result, larger production errors can be avoided.
- the method of the invention consists of the following steps: (a) providing a hollow fiber membrane bundle comprising a plurality of
- Hollow fiber membranes having a first end and a second end, wherein the openings of the lumens of the hollow fiber membranes at the first end of the hollow fiber membrane bundle open end, in particular liquid permeable, and at the second end of the hollow fiber membrane bundle closed at the end, in particular liquid-tight, are
- a hollow fiber membrane bundle comprising a plurality of hollow fiber membranes having a first end and a second end, the openings of the lumens of the hollow fiber membranes at the first end of the hollow fiber membrane bundle open end, in particular liquid permeable, and at the second end of the hollow fiber membrane bundle closed end, in particular liquid-tight configuration.
- the term "hollow-fiber membrane bundle” is to be understood as meaning a bundle of a multiplicity of hollow-fiber membranes.
- the hollow-fiber membrane is a membrane in the form of hollow filaments consisting of a porous material and having a substantially circular diameter, the wall thicknesses of such hollow-fiber membranes intended for dialysis, 10 to 100 ⁇ , depending on the membrane material, with luminal diameters of such hollow-fiber membranes lying between 150 ⁇ to 250 ⁇ , in particular between 180 ⁇ and 220 ⁇ , the fiber length is in the range of 150 ⁇ to 300mm, in particular between 250mm and 300mm
- the cavity of hollow fiber membranes can thereby of liquids
- provision is made for material to be separated on hollow-fiber membranes which, by utilizing a permeation of substances through a transmembrane mass transfer, from the outside to the inner cavity, or from the inner cavity to the outside of the hollow-fiber membrane
- Such hollow fiber membranes are typically used in therapeutic blood treatment
- the material of the hollow-fiber membranes can be selected from polymers, preferably from polysulfone, polyethersulfone, polyvinylpyrollidone, polypropylene, polyacrylonitrile, polyamide, polyvinylpyrrolidone, polyethylene ether, cellulose, Cellulose regenerate, cellulose acetate or mixtures thereof.
- Particular preference is given to hollow-fiber membranes which have a hydrophobic polymer material, for example polysulfone or polyethersulfone, and a hydrophilic polymer material, for example polyvinylpyrrolidone, in particular consisting thereof.
- the hollow fiber membrane has a plurality of pores, which serve to allow a mass transfer between the interior of the hollow fiber membrane and surrounding the hollow fiber membrane environment.
- the hollow interior of the hollow-fiber membrane is called "lumen.”
- the hollow-fiber membrane bundle which is used for the purposes of the present invention is not cast, ie, the ends of the hollow-fiber membrane bundle are not embedded in a plastic matrix.
- the term "lumen” is understood to mean a coherent cavity extending lengthwise inside the hollow-fiber membrane
- the lumen of hollow-fiber membranes is surrounded by the porous membrane wall, so that liquids which flow through the membrane
- the openings of the lumens at the fiber ends thereby form accesses to allow fluids, in particular liquids, to flow through the interior of the fiber Heat action are closed at the end, in particular, the lumens can be closed so that a respective end of the hollow fiber membrane is fluid, in particular liquid-tight.
- a hollow fiber membrane bundle preferably has at least 50 to 20,000 hollow fiber membranes. Typical diameters of hollow fiber membrane bundles are in the range of 15 mm to 50 mm.
- the hollow-fiber membrane bundle which is used in the method according to the invention is not cast, ie the ends of the hollow-fiber membrane bundle are not cast in a casting resin.
- the hollow fiber membrane bundle has a first end and a second end, wherein the first end is different from the second end.
- the first end of the hollow fiber membrane bundle has open hollow fiber membranes. In particular, the openings of the lumens of the hollow fiber membranes at the first end of the hollow fiber membrane bundle are open at the ends. This allows fluids and / or gas to escape from the lumen into the environment or enter the lumen from the environment.
- the starting point is a hollow-fiber membrane bundle which consists of a large number of hollow-fiber membranes whose permeation properties, in particular the clearance, are to be determined.
- Hollow fiber membrane bundles are obtained from the prior art production processes and used for the production of hollow fiber membrane filter modules.
- the openings of the lumens of the hollow fiber membranes in the hollow fiber membrane bundle are closed at one end.
- Methods for sealing the hollow fiber membranes at one end of the hollow fiber membrane bundle are known in the art.
- the hollow fibers can be closed by the action of heat, for example by heat radiation or thermal contact, by filling with waxes or plastics, or by laser radiation.
- a thermal contact method on an aluminum foil is preferred.
- closed means that the fiber ends are liquid-tight, so that no liquid can enter or exit the lumen of the fiber via the fiber end.
- the hollow-fiber membrane bundle is formed with the hollow-fiber membranes end-closed at the second end and hollow-fiber membranes open at the first end in an elongate, preferably vertically positioned housing.
- housing is to be understood as meaning a hollow body which is intended to receive a plurality of hollow-fiber membranes If a hollow-fiber membrane bundle consisting of a multiplicity of hollow-fiber membranes is introduced into a housing, a space in the housing remains the hollow fiber membranes and between the inside of the housing and the outside of the hollow fiber membranes, of liquids can be flowed through.
- Suitable housings can have an elongate extent, so that an extension axis of a housing is longer than a second and third extension axis and can thus be referred to as the longitudinal axis of the housing. According to the longitudinal extent of a proposed housing, this can be used in preferred orientations, vertical and horizontal.
- a corresponding housing is cylindrical, e.g. designed as a sleeve.
- Corresponding sleeve-shaped housings may be open to at least one of the ends, so that a hollow-fiber membrane bundle can be introduced into the sleeve. Then the housing can be closed or combined with appropriate end caps or fittings.
- Corresponding sleeves which serve as casings for hollow-fiber membrane bundles, are known from the construction of dialyzers in the prior art.
- Corresponding housings are preferably made of a rigid plastic material, e.g. Polycarbonate, polypropylene or polyoxymethylene, or of metals, e.g. Stainless steel or aluminum.
- the packing density of the hollow fiber membrane bundle formed in the housing is preferably 20 to 80%, preferably 50 to less than 65%.
- the elongate housing has a first end and a second end, the housing further having a fluid inlet at the first end and a fluid outlet at the second end.
- the arrangement of the hollow-fiber membrane bundle in the housing is such that the end-face open hollow fiber membranes are aligned for liquid inlet, and the end closed hollow fiber membranes are aligned to the liquid outlet.
- a first and a second test liquid are provided, wherein at least the first test liquid contains a test substance.
- the housing is filled with the first test liquid.
- the filling takes place so that existing air is displaced from the pores of the hollow-fiber membrane, the space between the hollow-fiber membranes and the lumen of the hollow-fiber membrane and is flushed out of the housing.
- the hollow fiber membrane bundle is completely flushed during the filling of the first test liquid, so that the hollow fiber membrane bundle is completely surrounded by the first test liquid.
- the filling of the housing it is provided to allow an excess of the first test liquid to flow over the liquid outlet of the housing.
- the volume rate of the incoming test liquid is adjusted so that the volume of the housing with the hollow fiber membrane bundle therein is exchanged once between 30 seconds and 5 minutes. In particular, it is provided to allow the test liquid to flow at a volume rate of 20 to 150 ml / min.
- the influx of the first test liquid is stopped and a second test liquid is added.
- the second test liquid is different from the first test liquid in at least the concentration of the test substance from the first test liquid.
- the second test liquid is distilled water.
- the concentration of the test substance is measured at the liquid outlet of the housing by suitable measuring means.
- the measuring means may be detectors which provide a concentration-dependent signal with respect to the test substance. Such detectors may be, for example, conductivity detectors or photometric detectors. Other detectors are well known in the art.
- the second test liquid does not contain the test substance or in a different concentration
- a concentration of the test substance which is generally different from the concentration of the test substance in the first test liquid is measured in the outflowing liquid at the liquid outlet of the housing.
- the concentration of the test substance in the second test liquid is present in a lower concentration than in the first test liquid, or not present, so that the observable concentration at the liquid outlet of the housing indicates a lower concentration with increasing inflow time of the second liquid time.
- the concentration determined by the measuring means in particular the determined concentration profile of the test substance at the liquid outlet, is characteristic of the permeation behavior of the examined hollow-fiber membrane in the hollow-fiber membrane bundle. Therefore, e.g. By changing the permeation properties of hollow fiber membranes during a production process of the hollow fiber membranes, conclusions about the quality of the production process or the resulting hollow fiber membranes are made.
- the hollow-fiber membrane bundle to be examined only has to be closed on one side and all further steps for producing a ready-to-use test filter module are dispensed with.
- a test filter module is understood to be a filter module which is similar to the structure of dialyzers but is used exclusively for determining the permeation properties of the hollow fiber membrane bundles produced and is subsequently disposed of.
- the usual manufacturing steps of the filter construction must be run through. That is, the hollow fiber membrane bundles are molded into the housing of the test filter modules and are end-sealed with a molding resin in the housing, which is disadvantageous.
- an effect of the invention according to the first aspect is to be seen in that the hollow fiber membranes can be examined in a short time, ie within a few minutes after their preparation in terms of their permeation property.
- the clearance in particular the diffusive clearance
- the clearance can be determined on the basis of a test substance by suitable evaluation of the measurement results obtained.
- Clearance, especially diffusive clearance is considered to be a characteristic permeation property of a hollow fiber membrane.
- the determined clearance and the determined diffusive clearance thus also serve as a measure of whether the production process proceeds according to predetermined process parameters, or whether the production process deviates unnoticed from the specification of the process parameters.
- the concentration of the test substance is measured repeatedly or continuously on at least one liquid outlet of the housing during the inflow of the second test liquid into the housing, as a function of time. From the measured values obtained or the course of the measured values, a concentration profile of the test substance is recorded at the liquid outlet.
- the second test liquid either has no test substance or the test substance is present in the second test liquid in a lower concentration than in the first test liquid, so that the recorded concentration curve represents a decreasing concentration of the test substance with time.
- the clearance, in particular the diffusive clearance can be determined by a characteristic curve parameter of the recorded concentration curve.
- a mathematical function is approximated to at least one section of the curve of the determined concentration curve. For example, known fit functions can serve as mathematical functions.
- a straight line can be adapted to a nearly linear section of the determined concentration curve.
- Other suitable fit functions may be exponential or sigmoidal functions.
- at least one characteristic parameter of the approximated mathematical function is determined. This can e.g. be the slope in a considered section of the concentration curve of the mathematical function.
- the determined characteristic parameter can serve to determine a second parameter which directly reflects the permeation property or the clearance, in particular the diffusive clearance.
- the determined characteristic curve parameter value was assigned to a specific value for the clearance, in particular the diffusive clearance, on the basis of previously determined calibration values.
- the previously determined calibration values can be in the form of tables and the clearance, in particular the diffusive clearance, can be determined from the characteristic parameter of the approximated mathematical function.
- the previously determined calibration values may e.g. serve a calibration function, or to create a calibration curve, so that an assignment of a first parameter that describes the mathematical approximation function with the clearance, in particular the diffusive clearance, is possible.
- the calibration curve is preferably created with the aid of hollow-fiber membranes whose clearance value was determined by known methods.
- the clearance can be determined, for example, on test filter modules which contain cast hollow-fiber membrane bundles of the hollow-fiber membrane to be examined, in accordance with the method specified in DIN / EN / ISO Standard 8637: 2014. Subsequently, identical Measure hollow fiber membrane bundle according to the method of the invention. From the determined concentration curve of the test substance, eg a characteristic slope value is determined, which is correlated with the already known clearance value of the test filter modules. Several such evaluations and correlations are performed on hollow fiber bundles with different pore nature of the hollow fiber membranes. From several of these correlations, a calibration curve is then created. It was found that a unique correlating curve can be established between the known clearance values and the evaluated curve parameter values.
- equation 1 offers itself as a mathematical function for rapid evaluation.
- A-i concerns the position of a straight line according to equation 1
- a 2 concerns the slope of the line
- Ci refers to the starting point of the curve
- C 2 indicates the X-axis section to the inflection point
- the corresponding calibration curves must also be made according to the same evaluation according to one of the equations 1 to 3.
- the characteristic curve parameter used for evaluating a hollow-fiber membrane bundle with an unknown clearance value is the same as that used to determine the corresponding calibration curve.
- the test substance of the test liquid is advantageously a substance whose concentration in the outflowing liquid is easily detectable and which can representatively reflect the examined permeation properties.
- sodium, creatinine, phosphate or vitamin B12 proves advantageous to determine the diffusive clearance of hollow fiber membrane.
- these substances are particularly preferred, since they are low molecular weight and therefore representative of the intrinsic molecular motion for the diffusive mass transport.
- the concentration of the test substances in the test liquid is chosen so that a good detectability is given.
- NaCl is to be used as the test substance in concentrations of 30 to 100 g / l, more preferably 70 to 90 g / l in order to be able to determine reproducible measurement results by measuring the conductivity at the liquid outlet of the housing of the measuring device .
- vitamin B12 is very well suited as a test substance, since vitamin B12 can be very well detected photometrically. Due to the higher molecular weight in comparison to NaCl, information about the pore size distribution of the hollow fiber membranes tested can additionally be obtained.
- vitamin B12 is used as the test substance in concentrations of 100 to 3000 mg / l, preferably 200 to 2000 mg / l, preferably 400 to 600 mg / l.
- the volume rate of the incoming second test liquid may be of importance for the process according to the invention.
- the accuracy of the measurement is ensured if at the liquid outlet of the test device, a volume rate of 10 to 120 ml / min, preferably 40 to 100 ml / min, preferably 60 to 80 ml / min is present.
- the packing density of the hollow-fiber membranes in the housing of the measuring device also influences the transmembrane pressure difference under flow conditions.
- hollow fiber membrane bundles having a number of hollow fiber membranes of from 50 to 20,000 hollow fiber membrane can be successfully tested, provided that a packing density of 20 to 80% in the housing of the test device is present. Below the packing density of 80%, it was found that no significant transmembrane pressure difference occurs in the flow state of the test method. This also avoids or reduces the convective mass transport across the membrane wall, which is particularly important for the determination of diffusive clearance.
- the invention relates to an apparatus with which the method according to at least one embodiment of the first aspect of the invention is executable.
- the device consists of at least one reservoir for receiving at least one liquid, in particular the first test liquid and / or the second test liquid, a measuring device comprising a housing having a first end and a second end for receiving a hollow fiber membrane bundle, wherein the first end the housing has at least one liquid inlet and the second end of the housing has at least one liquid outlet,
- connection device in particular pump means and fluid connections, for allowing at least one first test fluid and / or at least one second test fluid to flow from the at least one reservoir into the housing through the at least one fluid inlet at the first end of the housing,
- a detector for detecting the concentration of the at least one test substance, at least one liquid outlet at the second end of the housing.
- the invention relates to the use of a device according to the second aspect of the invention for carrying out a method according to the first aspect of the invention.
- the invention relates to the production of hollow fiber membrane filter modules, wherein the inventive method according to the First aspect of the invention is used to produce hollow fiber membrane having a predetermined permeation property.
- the method comprises the following steps:
- Permeation properties in particular the clearance of the hollow fiber membranes according to an embodiment of the first aspect of the invention, (f) Use of the hollow fiber membrane bundles for the construction of filter modules if it is determined that the one or more permeation properties lie in the at least one range of values defined in step (a) ,
- a range of values for a permeation property provided for the production of hollow fiber membranes is set.
- Such ranges of values may be, for example, a specific range for the clearance of a particular test substance, eg NaCl.
- Range of values is determined in advance in order to produce specific hollow-fiber membranes, which are suitable, for example, by their diffusive NaCl clearance for certain therapeutic procedures in dialysis.
- At least one production parameter is determined in order to be able to produce corresponding hollow-fiber membranes.
- the production parameters relate to those parameters which have an influence on the spinning process for producing the hollow-fiber membrane.
- the production parameters include, for example, the composition of the spinning solution, the composition of the internal coagulant, the temperature of the annular die through which the spinning solution is extruded, the extrusion rate, or the height of the precipitating gap.
- the variety of manufacturing parameters that affect the permeability property of hollow fiber membranes are described in the prior art.
- the hollow fiber membranes produced subsequently in accordance with the given manufacturing parameters and according to a spinning process are then bundled and provided in the form of hollow-fiber membrane bundles for the further production of the hollow-fiber membrane filter modules.
- a representative number of these hollow fiber membrane bundles are examined by the method of the present invention for determining one or more permeation properties according to an embodiment of the first aspect of the invention. It can thus be determined whether the one or more of the permeation properties lies within the predetermined range of values. In particular, it can thus be ascertained whether or not the hollow fiber membranes of the respective hollow-fiber membrane bundles are or are not in terms of, for example, clearance in the predetermined range of values.
- the manufacturing process can be controlled in a timely manner with the aid of the method according to the invention.
- it can be checked whether the hollow fiber membranes produced, for example, the predetermined Clearance range and whether the hollow-fiber membranes for the construction of hollow fiber membrane filter modules can be released.
- the above manufacturing method is particularly suitable for the production of hollow fiber membranes, which are prepared based on the membrane materials polysulfone and polyvinylpyrrolidone.
- the spinning solution used to make such hollow fiber membranes contains polysulfone (PSU) and polyvinylpyrrolidone (PVP), typically dissolved in polar aprotic solvents. Suitable solvents are, for example, N-methyl-pyrrolidone, dimethyl sulfoxide or di-methyl-acetamide. It has been found that mixtures of polysulfone / polyvinylpyrrolidone spinning solutions are particularly difficult to exactly observe the permeation properties, in particular the diffusive clearance, of the hollow-fiber membranes produced, since they are very sensitive to fluctuations in the production parameters.
- the present production process according to the invention has proven to be particularly advantageous for the production of PSU / PVP hollow-fiber membranes, since it offers the possibility of detecting the deviations caused by the change in the production parameters in the shortest possible time and adapting the production process accordingly.
- FIG. 1 shows an apparatus for determining a permeation property of hollow-fiber membranes on a hollow-fiber membrane bundle.
- the device shown consists of a reservoir with distilled water (1), which is controlled by a thermostat to a temperature of 25 ° C.
- the test fluid is an aqueous solution of the test substances NaCl at a concentration of 90 g / l and vitamin B12 at a concentration of 500 mg / l.
- a pump (3) With the help of a pump (3) either the water or the first test liquid can be transported.
- the flow leads to a closure which is sealed with an O-ring and which is attached to the lower end of a sleeve-shaped housing (4).
- the housing (4) in this case has the form of a sleeve, in which the hollow fiber membrane bundle (5) is introduced.
- the cap has a 4mm center hole through which the fluid enters the sleeve and serves as a fluid inlet (6).
- a hollow fiber membrane bundle is molded into the sleeve.
- the total length of the sleeve is 330 mm in the present embodiment and is open at the top. According to the present embodiment of Figure 1, this upper end with an inner diameter of 54 mm is slightly wider than the rest of the sleeve, which has an inner diameter of 34 mm.
- the hollow fiber membrane bundle itself is located in this narrower area and ends at its upper edge.
- An approximately 1 mm wide and 10 mm high annular gap (7) was milled out of the sleeve in the present embodiment, to obtain a flow for the test liquid.
- About 2 mm above is the liquid outlet (8) for sampling.
- the hollow fiber membrane bundle to be examined is melted with the aid of an aluminum foil on a hot plate at about 300 ° C. on one side (5b). After cooling the bundle, the aluminum foil is peeled off and the bundle is molded into the sleeve-shaped housing (4) as shown in FIG.
- the peristaltic pump is set to a flow rate of 70 ml / min and the housing (4) is first filled with the first test liquid.
- the open end (5a) of the hollow fiber membrane bundle (5) is adjacent to the bore (6).
- the delivery of the first test liquid to the delivery of the second test liquid is converted by means of the hose pump (3).
- the second test liquid is distilled water.
- distilled water now flows through the fluid inlet into the housing.
- a sample of 10 ml is taken every minute with the beginning of the inflow of the second test liquid.
- the measurement of the concentration can also take place continuously.
- the vitamin B12 concentration is determined in each sample by means of a photometer.
- the concentration of NaCl in the respective samples can be done by conductivity measurement.
- the substance concentrations of the respective samples determined from Example 2 are plotted against the time according to FIG. According to the present example, the concentration profile of the test substances NaCl and vitamin B12 at the liquid outlet, by a sigmoid function according to equation 3:
- the sigmoid function is mathematically approximated to the measured values by means of a software program, eg the program "Scilab", or the software program "Excel 2010".
- the parameters Ci to C 3 can be optimized with the help of an "add-in” with the designation "Solver” in such a way that the least possible deviation square is created the solution approach "GRG nonlinear” leads to good results.
- the value obtained for C 3 from Equation 3 is preferably used for the determination of diffusive clearance.
- Example 4 Comparison with Conventional Clearance Measurement Using the Example of Vitamin B12 Clearance
- dialyzers studied were dialyzers made by Fresenius Medical Care.
- Equation 3 was approximated to the determined measurement curve.
- the C 3 values obtained from the approximation of Equation 3 gave:
- the plot of the clearance values against the determined C 3 values is shown in FIG. 3.
- the plot shows a good correlation of the clearance values for vitamin B12 measured on the dialyzers and the C 3 values determined by the method according to the invention.
- the correlation can in turn by a suitable mathematical function and are used as a calibration curve or calibration function for further investigations.
- the traces of four hollow fiber membrane bundles F1 to F4 for vitamin B12 and sodium chloride are recorded.
- the clearance values of the hollow fiber membranes were previously determined on corresponding dialyzers with identical hollow fiber membranes by known methods, e.g. determined according to the method of the standard DIN EN ISO 8637 2014:
- the curve of the concentration curve over time can now be approximated with different functions. Different parameters are determined by regression or least-square adjustments, for example, using the Excel 2010 program. It has been shown that a linear regression can be sufficient:
- the readings between two and six minutes were used to do a regression.
- other measurement points can be selected. It is important that the same procedure is used between the creation of the calibration curve and the measurement for an unknown bundle.
- the formulas of Equation 1 and 2 have the advantage that the coefficients A 2, B ⁇ and B2 simply "Excel 2010" can be determined by adding the appropriate trend line in the respective software program, for example.
- a sigmoidal function describes an "S" curve and can typically be represented by Equation 3 as shown in Example 4.
- FIGS. 4 to 6 show the concentration course recorded on the hollow-fiber membrane F1 and the approximate mathematical functions from which the parameters A2, B2, and C3 are determined. Overall, the parameters listed in Table 4 were determined for the hollow-fiber membrane bundles F1 to F4:
- the corresponding calibration functions can be displayed. These can be used while maintaining the experimental and evaluation conditions to determine the clearance values of unknown hollow-fiber membranes. It has been shown in the examined hollow-fiber membrane bundles F1 to F4 that in particular the mathematical approximation of the measured concentration profile by a sigmoid function according to FIG. 6 is suitable for generating a calibration function.
- FIG. 7 shows a calibration line which was generated on the basis of the determined C3 values of the hollow-fiber membrane bundles F1 to F4.
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DE102016012730.9A DE102016012730A1 (en) | 2016-10-24 | 2016-10-24 | Method for determining a permeation property of hollow fiber membranes |
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DE102016012722A1 (en) * | 2016-10-24 | 2018-04-26 | Fresenius Medical Care Deutschland Gmbh | Method for determining a permeation property of hollow fiber membranes |
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CN112725914B (en) * | 2020-12-24 | 2022-01-28 | 西南科技大学 | Membrane silk collection device |
CN112808015A (en) * | 2020-12-25 | 2021-05-18 | 德蓝水技术股份有限公司 | Detection method and device for hollow fiber membrane |
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DE102021132060A1 (en) * | 2021-12-06 | 2023-06-07 | B.Braun Avitum Ag | filter module |
CN116297112B (en) * | 2023-05-25 | 2023-09-15 | 上海联风气体有限公司 | Gas permeability detection equipment and detection method for polymer film |
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