DE10340012A1 - Device for gas or liquid separation from microfluidic flow systems - Google Patents

Abstract

The invention relates to the technical field of microfluidic flow systems in which a gas or liquid separation takes place, which can be operated preferably position-independent. The device according to the invention is characterized by a combined use of a hydrophilic and hydrophobic membrane.

Description

The The invention relates to the technical field of microfluidic Flow systems in which a gas or liquid separation takes place, which are preferably position-independent can be operated.

Of the Scope of application of microfluidic flow systems is manifold and lies among other things in the analysis technology for medical diagnostics. In particular, in modern diagnostics finds the use here microfluidic systems frequently Application. This is i.a. This is due to the fact that it is modern Diagnostics more and more aspirations, the condition of a patient continuously monitor. Due to continuous analysis results, it is thus possible to have a achieve optimal diagnosis and therapy for the patient individually to be able to. For one continuous monitoring However, if the patient is in a condition, the patient must be on a permanent basis Examine examination so that the patient is forced to enter appropriate analysis system always carry with you. Are such Long-term examinations not only for inpatient stay provided in a hospital, but should also be used for everyday life Patients prove to be fit, thereby conditionally high demands to a comfortable handling of the analysis system. From this results compelling, the size of the analytical systems used Minimize as far as possible, so that the patient the system in everyday life inconspicuous and little disturbing carry with them can. The patient should hereby a small as well as robust Device for disposal be placed so that the person concerned in their freedom of movement only minimally restricted becomes.

A continuous or at least quasi-continuous monitoring a patient condition even outside the inpatient area is in medicine, especially in the field of diabetes monitoring desirable. Through continuous monitoring of the glucose level on the one hand threatening hypoglycemic Conditions, which lead to the death of the patient can, be recognized in time as well as on the other hand, a warning hyperglycemic States take place, usually with long-term damage (Blindness, gangrene, etc.) are connected. Therefore, there have been considerable efforts lately been undertaken, a continuous monitoring of blood sugar levels to enable a patient. The following is without limitation to the general public the use of microfluidic flow systems using the example of glucose concentration measurement closer to diabetes described.

conventional Ways to monitor the glucose level of blood are often done portable devices, so-called blood glucose meters, realized. A disadvantage of this method of analysis, however, is that first a Wound for blood collection into a body part of the patient must be before the patient subsequently changes the blood to an analyte-specific Test element can give up. The test element is in a portable Analyzer which the patient must always carry with him, introduced and analyzed. The complex as well as painful procedure limits the Scope of application usually on individual measurements and is therefore especially for Patients with severe diabetes only inadequate. To one continuous monitoring the glucose content, the analysis system must consequently a stable one Analysis of the body fluid of the Ensure patients can.

in the The state of the art sets the microdialysis today reliable Method to continuously monitor analyte concentrations. The patient may be small in size of the analysis system this unobtrusive and without big ones Disability in everyday life and carry it to regular inspection apply. For this a small microdialysis probe becomes easy and for the patient little traumatic in the body introduced. For analyte determination, a perfusion fluid is passed through a catheter passed, with the perfusion fluid in an exchange area in contact with a body fluid located and absorbs substances from the body fluid. This enriched perfusion, the dialysate is then forwarded to an analysis unit, the z. B. the glucose concentration in the dialysate is missing. In the state In the art, a number of microdialysis probes are known for the this place representative only to the, in the German Patent application 10010587.4 described, reference is made.

at microdialysis, however, has numerous requirements in the art Area of fluid handling to the functioning of the microdialysis system guarantee to be able to. Among other things, must be for a precise analysis result the liquid within the microdialysis bubble-free, since only so a reproducible liquid transport takes place and an exact analyte determination is possible.

The prior art discloses several possibilities for gas separation from liquids, but these devices are not suitable for use in the microfluidic area. Furthermore, most systems can not be operated independently of location. However, the purpose of microsystems in medical diagnostics is to provide a portable analysis system which allows permanent monitoring. However, this requires, inter alia, a position-independent operation of the transportable system.

The patent EP 0 552 090 B1 discloses a device for separating gases from liquids, which can be operated independently of position due to a corresponding liquid guide. However, the device is not intended for use in the area of the microfluidic flow system. In the device, the liquid is passed through fluid channels in which a gas separation takes place. The channels are connected to a hydrophobic membrane so that the gas can escape through the hydrophobic membrane into the atmosphere of the environment. A disadvantage of the device described is the complex structure of the system, which is reflected, inter alia, in the production costs for such a device. This is particularly important if such devices are provided in a designated application area as exchangeable disposable items. In the field of microdialysis, however, experience has shown that parts which come into contact with liquids, for example gas separators, are frequently used in the form of a disposable microdevice. An application of the described system for a microdialysis device would therefore prove to be too complicated and expensive in the described example.

Furthermore, in the document EP 0 787 503 discloses a system for position-independent gas separation in which gas can escape from a liquid through a hydrophobic membrane. Although the system initially has a simple structure, but adversely affects the functionality of the device. Due to the simple construction of the device, there is, inter alia, in the region of the membrane system, no sufficient reduction of the flow rate, so that complete gas separation from the liquid can not be ensured. Consequently, such a device proves to be inadequate, in particular for systems in which an exactly reproducible liquid transport must be present.

Of the Invention is the object of a device for gas or liquid separation in a microfluidic system. The system should be in spite of a simple structure a substantially sufficient Gas or liquid separation from a fluid and preferably position-independent can be operated.

The This invention is described by the independent claims. Advantageous embodiments arise according to the dependent claims.

The The invention includes a device for gas separation in one microfluidic system. The device has a fluidic supply line which contains a hydrophobic membrane in at least one area can escape through the gas within the supply line. Furthermore The device includes a drain with a hydrophilic membrane. Inlet and outlet of the device are so fluidly together connected to a liquid, which flows through the supply line into the drain, the hydrophilic membrane must happen. The hydrophilic membrane is essentially only for liquids Permeable, so that gas is held back in the supply line while the Liquid through drain the drain can.

Of Another object of the invention is a device for liquid separation from a microfluidic system. The device has analog to the gas separation system, a fluidic supply and discharge on, which are also each provided with a membrane. in this connection However, the fluidic supply line is complementary to the device for gas separation, a hydrophilic membrane. Accordingly, the Derive a hydrophobic membrane. Inlet and outlet are then so fluidly connected to each other, that is a gas in the system is transported and flows from the supply line to the derivative, the hydrophobic membrane must pass.

The systems according to the invention to the liquid or gas separation is by the combination of a hydrophilic Membrane marked with a hydrophobic membrane. To this One way is to separate different phases of a fluid safely ensured by a simple structure.

in this connection causes the membrane of the derivative the actual phase separation step, there exclusively a phase of the fluid, for the membrane is permeable, through the membrane and thus through drain the drain can. The phase to be separated is thus initially within the supply line retained where it can then escape through the membrane of the supply line. The Membrane of the supply prevents in this way too much enrichment the phase to be separated within the supply line, which affect the functionality of the device could. A reliable one Operating state of the device is thus guaranteed long term.

A combination of the hydrophilic or hydrophobic membranes and consequently the structure of the device can be carried out according to the invention in many ways, so that the invention to spe spe cifical embodiment is limited. For example, a device according to the invention can be integrated into a hose line, wherein a first region of the hose line, which can be regarded as a supply line of the device, then has a corresponding membrane. Within the tube, a membrane is further integrated in such a way that the membrane in the form of a semipermeable separating layer separates the first and a second region of the tube from each other. The first and the second region then represent the supply and discharge of the system. According to the invention, the membrane must be integrated in the tube in such a way that a fluidic seal between the membrane and the tube takes place so that only fluid for which the membrane is permeable , in the area of the hose (discharge) can flow away beyond the membrane. Of course, it is also conceivable to initially implement supply and discharge as independent components before subsequently the elements are fluidly connected to each other during a manufacturing process. In the example described then z. B. first, a first end of the hose, which is provided as a derivative, closed with a membrane and then connected to another end of the hose, the supply line. Here are the ends of the inlet and outlet z. B. glued together.

When Membrane in the invention may use any materials which are adapted to the field of application permeability for only one Phase of a fluid. Furthermore, the material must be on the respective field of application be adjusted so that fluid and device inert to each other. Aging effects or Swelling effects of the membranes can thus minimized as far as possible. Exemplary prove to be a hydrophobic Membrane the materials PP (polypropylene) or PTFE (poly-tetrafluoroethylene) as suitable as well as PA (polyamide) or PVDF (polyvinylidene fluoride) or PVP (polyvinylpyrrolydone) can be used as a hydrophilic material can. As hydrophilic Memrane are referred to, when in contact with water Spontaneously absorb this into their pores. This may be due to the properties of the base material, an alloy component (so-called polymer alloys) or by a coating of the pore surfaces with a hydrophilic Layer e.g. a surfactant an uncrosslinked or a crosslinked hydrophilic polymer (e.g., hydroxypropylene cellulose or PVP). Hydrophobic refers to membranes that are not spontaneous due to water be wetted. Such membranes are obtained either from hydrophobic base materials, such as. PP (poly-propylene) or PTFE (poly-tetrafluoroethylene) or by coating the pore surfaces with a hydrophobic layer e.g. a perfluoro compound or a silane. The pore sizes of Membranes can also be adapted to the respective field of application, so that on the one hand ensures a sufficient separation of a fluid phase and, on the other hand, no clogging of the pores. The separation of the finest gas bubbles or Flussigkeitgropfen drops it in the field of microfiltration. The pore sizes in microfiltration included one Range down with ultrafiltration and up overlaps with the fine filtration. Usually are the pore sizes for microfiltration between 0.1 μm and 10 μm. The choice of pore fineness in the context of the invention is directed both according to availability and compatibility materials, as well as the intended operating conditions. The smaller the pores chosen be, the finer gas bubbles or liquid droplets can be deposited, wherein at the same time, however, as a rule, the permeability of the membrane decreases. Especially for membranes that liquid permeable, this can be a limiting factor. By larger membrane areas can however, this effect will be compensated. Typical pore size, the in the field of microdialysis prove to be suitable for. B. in the range of 0.1 microns up to 0.5 μm.

The inventive device can over it Beyond that, in addition to a sterile filtration of the fluid, as will be explained in more detail below, perform. Therefor prove membranes with a pore size of 0.45 or 0.22 microns as advantageous.

In an advantageous embodiment are used as membranes microfiltration hollow fiber membrane, wherein the hydrophobic and / or hydrophilic membrane is configured in the form of a hollow-fiber membrane can be. Will both the hydrophilic and the hydrophobic membrane used in the form of a hollow fiber, the membranes are intertwined arranged so that z. B. in a device for gas separation the hydrophilic microfiltration membrane at least partially within a portion of the hydrophobic microfiltration membrane inserted is, with the respective end of the membranes with the inlet and outlet is sealed fluidly by gluing. In the example described possesses the hydrophilic microfiltration hollow fiber membrane thus has an outer diameter, which is smaller than the inner diameter of the hydrophobic microfiltration membrane.

The device according to the invention has a simple structure and can be produced without problems even on a microscale by commercially available components. For example, a commercially available PTFE hollow fiber membrane (polytetrafluoroethylene) is used for this purpose. The outside diameter ser such a hollow membrane is then z. B. 1.7 mm, resulting in an inner diameter of about 1 mm. A corresponding microporous hydrophilic PVDF hollow-fiber membrane (polyvinylidene fluoride) then has an outer diameter, reduced to about 0.45 mm corresponding to the hydrophobic membrane, and an inner diameter reduced by about 0.1 mm. Such membranes are described as described, for. B. from the companies Gore in Munich or the company Memtec Corp. Delivered to Australia. As the inlet and / or outlet of the device, for example, silicone tubes are used, in which the membranes are integrated as described. Of course, the supply and / or discharge of the device can be completely formed by the hollow fiber membrane, so that no additional elements for the supply and discharge are provided. If such a device is integrated, for example, in a microdialysis system, the supply and discharge of the device in the form of hollow fiber membranes is in each case directly connected fluidically to the hoses of the microdialysis system, for example via a two-component adhesive. In a device as described, then after curing of the adhesive, the hydrophilic membrane is inserted into the end of the hydrophobic membrane. The end of the hydrophobic membrane is then also bonded to the end of the hydrophilic membrane. In the example given, the adhesive is used both as a mechanical connecting element and as a fluidic seal. Advantageously, however, the device is reversibly connected to the microdialysis system, so that the device can be replaced as needed as a disposable unit.

Becomes The device used in the field of microdialysis should continue in the selection of materials used to make the systems be used, be careful that the material with the dialysate or microperfusate is compatible and none changes comes, which determines the concentration of the analyte or the Analyze analysis as such unpredictably.

tries with devices as described above have shown that in a fluid of an air-water mixture in the volume ratio of 1: 1 and a flow rate from 0.3 to 3 μl / m, one essentially complete Separation of air bubbles and water could be achieved.

Should the application of the device also for much higher flow rates be suitable, so in an advantageous embodiment, the flow rate in the area of the membranes first be slowed down. Will the length and / or the diameter of the membranes used so far increased that it to reduce the flow rate comes, and thus a sufficiently long residence time of the fluid in Exchange area guaranteed is, thereby the phase separation is supported.

In a preferred embodiment includes a microfluidic flow system with a device according to the invention continue a pump, by means of which the flow rate of the liquid is controlled. This way, in addition to having an influence on the Phase separation also an exact determination of the amount of liquid flowing through possible, wherein a determination of the fluid flow z. B. in particular at the measurement of analysis concentrations proves necessary. Becomes a device as described, for gas deposition in the area used the microdialysis and the device in the flow direction installed in front of the pump, it is ensured that no gas bubbles promoted which are a measured volume of liquid distort would. Based on an exact volume determination of the transported Dialysate can now be calculated an exact glucose concentration.

The System can about it In addition, preferably position-independent be operated, so that the device also for everyday use in the field a continuous diagnostic is suitable. For a location-independent operation ensure the device to be able to has the supply line in substantially all directions corresponding membrane system. The phase to be separated can then independent from the location of the device and the density of the to be separated Phase from the supply line through the membrane or the membrane system escape.

Tries, Consequently, with the systems described, the system according to the invention, despite the simple construction a substantially complete separation two phases of a fluid allowed and the operating conditions z. B. in a microdialysis system in full.

For use in the field of microdialysis, the system is further connected to a microdialysis probe and a liquid reservoir, as described in more detail below. In a preferred embodiment, the device according to the invention is positioned upstream of the microdialysis probe in the microdialysis system. In this case, the microanalysis system serves - as already described - to determine at least one concentration of an analyte in a body fluid. The term analyte in the context of the present invention includes all possible analytes such. Glucose, lactate, proteins, minerals and neurotransmitters. The term "body fluid" in the context of the present invention, all possible body fluids such as in particular intersti include fluid, blood and cerebral fluid. The system is designed primarily for continuous human diagnostics, but other possible applications, such B. on the animal, be included. In the context of the present invention, the term microdialysis system is used for an embodiment in which a mass transfer between the outer space and a perfusion fluid takes place via a membrane. Microdialysis systems known in the art are disclosed, for example, in the documents EP 0 649 628 and US 5,174,291 described. However, the device is suitable for. As well as for processes which are generally referred to as ultrafiltration. Here, a filtration of the body fluid surrounding the system is first achieved by a membrane in the ultrafiltration system. Above all, the membrane of ultrafiltration serves to exclude higher-molecular substances that interfere with the analysis or cause aging of the sensor. The documents US 4,777,953 and US 4,832,034 describe by way of example the method of ultrafiltration. The exchange region in which the membrane of the ultrafiltration system is present preferably has an elongated shape so that it has the shape of a rod. For example, the end of the rod may be pointed so as to facilitate insertion into the human body. In the prior art exist a variety of different types of application kits, which will not be discussed in more detail here. It should be noted only by reference to documents WO 97/14468 (TFX Medical Inc.) and WO 95/20991 (CMA Microdialysis Holding AB).

At least one sensor for detecting an analyte is arranged in the measuring area of the analysis unit. For the detection of glucose, for. Example, a metal electrode can be used, which is coated on its surface with glucose oxidase or a glucoseoxidasehaltigen reagent mixture. However, it is also possible, for example, to add dissolved glucose oxidase into the measuring cell. This measuring method is z. In the document EP B 0 393 054 described. In this case, a bubble-free transport of the liquid is described as an essential aspect for an exact detection of the analyte concentration, so that no gas is present at the electrodes, which would lead to undefined states.

Farther is it for an implementation a microdialysis advantageous, a reservoir for perfusion fluid and / or a reservoir for receiving dialysate after analysis to provide, directly or via a channel is connected to the exchange area. For transport of perfusion fluid through the exchange area and towards the sensor area is a pump intended. Such a pump can, for example, in printing operation work and thus liquid from the reservoir for perfusion press out or else she can work in suction mode and liquid pass through the system. Furthermore, a pump, for example be arranged so that they are liquid withdraws from the fluid reservoir and supplies the exchange area. Latter Variant can be carried out analogously to a conventional peristaltic pump, at the one by the outside engaging roller element fluid by squeezing a compressible portion of the fluid channel is moved. Corresponding systems, for example, are in the field the "implanted delivery devices "in use. By way of example, reference should be made here to the document WO99 / 41606 from the Range of microdialysis, referenced. This shows up in the state the technique that in microdialysis, for example, channels with a Diameter can be used in the range of 10-1000 microns, where a channel length in the range of a few centimeters. For a linear flow rates of about 1 cm / min thus prove pressures in the range of a few millibars as adequate. Furthermore, such systems have one with the sensor connected evaluation unit, which is used to convert sensor signals serve in concentration values of the analyte.

For the device for the separation of liquid a gas also offers a variety of possible applications, such as B. in the field of medical technology. For example, done an application in the field of artificial Ventilation, where the device for removal of fluid drops from a humidified gas stream, can be used. Further Application areas are z. B. Analysis systems used for the analysis of Breathing air can be used.

Especially in the field of application of the analysis shows that it often leads to measured value errors caused by liquid droplets in the gas analyzer. These arise, for example, in which the gas exhaled by humans in the analysis system undergoes a cooling of the body temperature. Upon contact with the analysis system, condensation of the water contained in the respiratory air takes place. A device according to the invention makes it possible, for example, to separate water in liquid form from the respiratory air before it is passed into a CO ₂ analyzer. If the device - as described - used for liquid separation, it is advantageous that the liquid-permeable membrane is wetted with liquid before use of the device, so that at the beginning of the measurement, no gas can escape through the dry membrane. An exact analysis of a gas flow is thus ensured during the entire measurement process.

In addition, there are more areas of application in analytics and in the synthesis of highly pure substances, which are each working on a microscale, so that the devices according to the invention are generally not limited to any particular field of application.

in principle are also complementary to the applications described complementary uses conceivable, so that z. B. a device according to the invention also for gassing a liquid can be used. Trials have shown that at one before degas solution, at a flow rate of 1.2 μl / min by the device according to the invention flows, a comparable fumigation of the liquid can be obtained as they do conventionally by fumigation with a silicone tube the same diameter is achieved.

The inventive system can preferably be operated at atmospheric pressure, the usual Variations in the ambient pressure, the deposition of the separated Essentially not adversely affect phase.

The inventive device is still not on a given application time in a system limited, as always a derivative of the phase to be separated by the supply line he follows. Nevertheless, it is important to ensure that the functionality the device is always given. Here it is u. a. conceivable that it pollutes the membrane and thus constipation the pores can come that affect the functioning of the device; especially when the device in addition to the function of the invention for gas or liquid separation still for the separation of particles within the fluid serves. In this case, particles that are larger than the pore diameter are retained in the supply line of the system, leaving the fluid Essentially particle-free, the derivative happens. For example the device for the separation of microorganisms from a Serve fluid. Under these circumstances Thus, the device is also used for the sterilization of fluids. Such an additional function However, the device may cause the pollution described above in particular lead the membrane of the derivative, so that thereby the life the device may be limited according to the field of application is. To the functionality to ensure the device is in an advantageous embodiment a sensor integrated in the microfluidic flow system, the the fluid is missing after the phase separation step. Such a Sensor is z. B. within the derivative or generally downstream. the device according to the invention within the system conceivable, and z. B. in a microdialysis probe will be realized. For example, the sensor then serves for detection of bubbles or liquid drops in the fluid or for the detection of the flow velocity in the event of constipation the membranes would fall accordingly. A sensor monitors the function the device according to the invention, it is thus possible for the user to replace the system as soon as the function of the Gas or liquid separation is no longer guaranteed to a satisfactory extent. The device according to the invention is then advantageously designed as a disposable and can in simply be replaced with the system intended for use. Naturally It is also conceivable, the device at a pollution of the Membrane by appropriate rinsing processes again to clean. Regarding the simple and inexpensive However, the manufacture of the device proves the use of the Systems as disposable as preferred.

following will be explained with reference to the figures by way of example of the subject invention.

1 : Device for gas separation with inlet and outlet in the form of a hollow-fiber membrane.

2 : Device for gas separation with only one hollow-fiber membrane.

1 shows a device ( 10 ) for gas separation, in a hose system ( 1 ) is integrated. The hose system ( 1 ) is fluidic with the device ( 10 ) is connected to the gas separation and is applied via an adhesive ( 5 ) connected to the device. Here, the adhesive ( 5 ) is chosen so that it fluidically seals the system and thus impermeable to the fluid to be transported ( 4 ) within the system. The device ( 10 ) has a supply line ( 2 ), which in the example shown is completely formed by a hydrophobic hollow-fiber membrane. Within the hydrophobic hollow-fiber membrane, the derivative ( 3 ), which is also completely formed by a hydrophilic hollow fiber membrane. If liquid passes through the region of the tube system in which the gas separation device is integrated, and if gas is contained in the liquid, a separation of the liquid from the gas phase takes place in the region of the hydrophilic membrane. In this case, only the fluid in the liquid state through the hydrophilic membrane to pass the derivative and thus into the hose area ( 1b ) reach. The bubbles contained in the liquid ( 6 ) thus accumulate within the feed line in front of the hydrophilic membrane, where they pass through the hydrophobic membrane of the feed line ( 2 ) can escape. In this case, the hyrophobic membrane extends in all spatial directions, so that an escape of the gas bubbles regardless of the bearings of the Device is possible.

2 shows a further device according to the invention for gas separation. The device has a supply line ( 2 ), which in a front region a hydrophobic membrane ( 2a ) owns. The supply line is fluidic with the discharge ( 3 ), which at the front end by a hydrophilic membrane ( 3a ) is closed. Will liquid ( 4 ) transported from the supply line to the discharge line, this must be at the front end of the discharge ( 3 ) positioned hydrophilic membrane ( 3a ), which extends through the hose system in the form of a separating layer and thus separates the supply line from the discharge line. The hydrophilic membrane ( 3a ) is preferably a polymeric material ( 5 ) with the derivative ( 3 ) glued or welded. It is at a distance from the hydrophobic membrane ( 2a ), which preferably lies between 0 and at most 10 times, preferably 2 times, in particular 0.5 times, the diameter of the feed or discharge line. Gas bubbles which accumulate within the liquid in the front region of the feed line can pass through the hydrophobic membrane ( 2a ), analogous to 1 escape, causing it to degas the liquid ( 4 ) comes.

The shown embodiments are exemplary and within the scope of the invention in many ways variable. Inventions here allowed a combined arrangement of a hydrophobic and hydrophilic membrane a phase separation for Microfluidic systems.

Claims (13)

Microfluidic device for gas separation from a microfluidic flow system including - a fluidic Supply line, the at least in one area a hydrophobic membrane through which gas can escape in the supply line as well - a derivative, which has a hydrophilic membrane in at least one area, which essentially for a liquid permeable and for a gas is impermeable, being - Inlet and outlet in the Are fluidly connected with each other, that a liquid, which flows from the supply line into the discharge, the hydrophilic membrane must happen. Microfluidic device for liquid separation from a microfluidic flow system, including - a fluidic Supply line, the at least in one area a hydrophilic membrane through, through the liquid in the supply line can escape as well - a derivation that at least in a region having a hydrophobic membrane which is substantially for a Gas permeable and for a liquid impermeable is, where - and drain are fluidly connected together in such a way that a gas that flows from the supply line into the drain, the hydrophobic membrane must pass. Apparatus according to claim 1 or 2, wherein the supply line essentially one or more membranes in all spatial directions having. Apparatus according to claim 1 or 2, wherein the hydrophobic Membrane is a hollow fiber membrane. Apparatus according to claim 1, 2 or 4, wherein the hydrophilic membrane is a hollow fiber membrane. Apparatus according to claim 1, wherein the hydrophilic Membrane disposed within a region of the hydrophobic membrane is. Apparatus according to claim 2, wherein the hydrophobic Membrane disposed within a region of the hydrophilic membrane is. Apparatus according to claim 1 or 2, wherein the hydrophobic and hydrophilic membranes are arranged in close proximity to each other and the distance of the membrane from each other is less than 10 times Diameter of the supply or discharge lines is. Apparatus according to claim 8, wherein the hydrophobic and hydrophilic membranes are arranged in close proximity to each other and the distance between the membrane to each other less than 2 times, advantageously less than 0.5 times the diameter of the inlet or outlet. Apparatus according to claim 1 or 2, which in a Hose line is integrated. Apparatus according to claim 1 or 2, which provide so is that in the area of the membrane of the supply line, the flow rate of a fluid is lowered. Apparatus according to claim 1 which is in an ultrafiltration system is used. Apparatus according to claim 1, which is in a microdialysis system is used.