WO2005028066A1

WO2005028066A1 - Device for separating gas or liquid from microfluidic through-flow systems

Info

Publication number: WO2005028066A1
Application number: PCT/EP2004/009430
Authority: WO
Inventors: Herbert Harttig; Ulrike Kamecke
Original assignee: Roche Diagnostics Gmbh; F. Hoffmann-La Roche Ag
Priority date: 2003-08-30
Filing date: 2004-08-24
Publication date: 2005-03-31
Also published as: DE10340012A1

Abstract

The invention relates to the technical field of microfluidic through-flow systems involving the separation of gas or liquid, preferably carried out irrespective of position. The inventive device is characterized by the combined use of a hydrophilic and hydrophobic membrane.

Description

Device for gas or liquid separation from microfluidic flow systems

The invention relates to the technical field of microfluidic flow systems in which gas or liquid separation takes place, which can preferably be operated independently of the position.

The area of application of microfluidic flow systems is diverse and includes analysis technology for medical diagnostics. Especially in modern diagnostics, microfluidic systems are often used

Application. This includes justified by the fact that in modern diagnostics there are more and more efforts to continuously monitor a patient's condition. Based on continuous analysis results, it is therefore possible to achieve an optimal diagnosis and therapy for the patient individually. For continuous monitoring of a patient's condition, however, the patient must undergo a continuous examination, so that the patient is forced to always carry an appropriate analysis system with him. If such long-term examinations are not only intended for inpatient stays in a hospital, but should also prove to be suitable for a patient's everyday life, this places high demands on comfortable handling of the analysis system. This means that the size of the analysis systems used must be minimized as much as possible, so that the patient can

System can be inconspicuous and less disruptive in everyday life. The patient should be provided with a device that is as small and robust as possible, so that the person concerned is only minimally restricted in his freedom of movement.

Continuous or at least quasi-continuous monitoring of a patient's condition, even outside the inpatient area, is desirable in medicine, particularly in the field of diabetes monitoring. Through continuous monitoring of the glucose level, on the one hand, impending hypoglycemic conditions that can lead to the patient's death can be recognized in good time, and on the other hand, a warning of hyperglycemic conditions take place, which are usually associated with long-term damage (blindness, gangrene, etc.). Therefore, considerable efforts have recently been made to enable continuous monitoring of a patient's blood sugar level. In the following, the use of micofluidic flow systems will be described in more detail using the example of measuring glucose concentration in diabetes without being restricted to the general public.

Conventional ways of monitoring the glucose content of blood are often implemented using portable devices, so-called blood glucose meters. A disadvantage of this analysis method, however, is that a wound must first be created for drawing blood into a part of the patient's body before the patient can then apply the blood to an analyte-specific test element. The test element is inserted and analyzed in a portable analysis device, which the patient must always carry with him. The complex and painful procedure generally limits the area of application to individual measurements and is therefore insufficient, especially for patients with severe diabetes. In order to continuously monitor the glucose content, the analysis system must be able to ensure a constant analysis of the patient's body fluid.

In the state of the art, microdialysis technology is reliable today

Procedures to continuously monitor analyte concentrations. With a small size of the analysis system, the patient can carry it inconspicuously and without major disabilities in everyday life and use it for regular checks. For this purpose, a small microdialysis probe is inserted into the body easily and not very traumatically for the patient. A

Perfusion fluid passed through a catheter, the perfusion fluid being in contact with a body fluid in an exchange area and absorbing substances from the body fluid. This enriched perfusion liquid, the dialysate, is then passed on to an analysis unit which, for. B. missed the glucose concentration in the dialysate. A number of microdialysis probes are known in the prior art, for which reference is made here only to the arrangement described in German patent application 10010587.4.

With microdialysis, however, there are numerous requirements in the field of fluid handling in order to be able to guarantee the functionality of the microdialysis system. Among other things, the liquid has to be used for an exact analysis result are present in the microdialysis without bubbles, as this is the only way to ensure reproducible liquid transport and exact analyte determination is possible.

The prior art discloses several options for gas separation from liquids, but these devices are not suitable for use in the microfluidic field. Furthermore, most systems cannot be operated regardless of the location. However, the purpose of microsystems in medical diagnostics is to provide a portable analysis system that allows permanent monitoring. However, this may require. a. operation of the portable system regardless of location.

Patent EP 0 552 090 B1 discloses a device for separating gases from liquids, which can be operated regardless of the position due to a corresponding liquid guidance. However, the device is not intended for use in the area of the microfluidic flow system. In the device, the liquid is passed through liquid channels in which 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 u. a. reflects the manufacturing cost of such a device. This is particularly important if such devices are provided in a

Field of application are provided as interchangeable disposable items. In the area of microdialysis in particular, experience has shown that parts in contact with liquid such as Gas separators are often used in the form of a disposable microdevice. An application of the described system for a microdialysis device would therefore prove to be too complex and expensive in the example described.

Furthermore, 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. The system initially has a simple structure, but it adversely affects the functionality of the device. Due to the simple structure of the device, there is no sufficient reduction in the flow rate in the area of the membrane system, so that complete gas separation from the liquid cannot be guaranteed. Such a device consequently proves to be inadequate, in particular for systems in which an exactly reproducible liquid transport must be provided. The invention has for its object to provide a device for gas or liquid separation in a microfluidic system. In spite of a simple construction, the system should ensure an essentially sufficient gas or liquid separation from a fluid and should preferably be able to be operated independently of the position.

The invention is described by the independent claims. Advantageous embodiments result from the dependent claims.

The invention includes a device for gas separation in a microfluidic system. The device has a fluidic feed line which contains at least in one area a hydrophobic membrane through which gas can escape within the feed line. Furthermore, the device includes a drain with a hydrophilic membrane. The supply and discharge lines of the device are fluidly connected to one another in such a way that a liquid that flows through the supply line into the discharge line must pass through the hydrophilic membrane. The hydrophilic membrane is essentially only permeable to liquids, so that gas is retained in the feed line while the liquid can flow off through the discharge line.

The invention furthermore relates to a device for liquid separation from a microfluidic system. Analogous to the system for gas separation, the device has a fluid supply and discharge line, which are also each provided with a membrane. Here, however, the fluidic feed line contains a hydrophilic membrane complementary to the device for gas separation. Accordingly, the derivation has a hydrophobic membrane. The supply and discharge lines are then fluidly connected to one another in such a way that a gas which is transported in the system and flows from the supply line to the discharge line must pass through the hydrophobic membrane.

The systems for liquid or gas separation according to the invention are characterized by the combination of a hydrophilic membrane with a hydrophobic membrane. In this way, a separation of different phases of a fluid is guaranteed by a simple structure. Here, the membrane of the derivation determines the actual phase separation step, since only one phase of the fluid, for which the membrane is permeable, can flow through the membrane and consequently through the derivation. The phase to be separated is thus initially retained within the feed line, where it can then escape through the feed line membrane. In this way, the membrane of the feed line prevents the phase to be separated from accumulating too much within the feed line, which could impair the functionality of the device. A reliable operating state of the device is thus also guaranteed in the long term.

A combination of the hydrophilic or hydrophobic membranes and consequently the construction of the device can be carried out according to the invention in a variety of ways, so that the invention is not restricted to any specific embodiment. For example, a device according to the invention can be integrated into a hose line, a first area of the hose line, which can be regarded as the feed line of the device, then having a corresponding membrane. Furthermore, a membrane is integrated within the hose in such a way that the membrane separates the first and a second region of the hose from one another in the form of a semi-permeable separating layer. The first and the second area then represent the supply and discharge of the system. According to the invention, the membrane must be integrated in the hose in such a way that a fluidic seal between the membrane and

Hose is made so that only fluid for which the membrane is permeable can flow into the area of the hose (discharge line) beyond the membrane. It is of course also conceivable to first implement supply and discharge as mutually independent components before the elements are then fluidly connected to one another during a production process. In the example described, z. B. first a first hose end, which is provided as a derivative, closed with a membrane and then connected to a further hose end, the feed line. Here, the ends of the feed or discharge z. B. glued together.

Any material can be used as the membrane in the context of the invention which has a corresponding permeability for only one phase of a fluid which is adapted to the field of application. Furthermore, the material must be matched to the respective field of application so that the fluid and the device are inert to one another. Aging effects or swelling effects of the membranes can thus be minimized as far as possible. Exemplary for one hydrophobic membrane the materials PP (polypropylene) or PTFE (poly-tetrafluoroethylene) as suitable and PA (polyamide) or PVDF (polyvinylidene fluoride) or PVP (polyvinyl pyrrolydone) can be used as the hydrophilic material. Membranes are called hydrophilic, which spontaneously absorb water into their pores when they come into contact with water. This can take place through the properties of the base material, an alloy component (so-called polymer alloys) or by coating the pore surfaces with a hydrophilic layer, for example a surfactant, an uncrosslinked or a crosslinked hydrophilic polymer (for example hydroxypropylene cellulose or PVP). Membranes that are not spontaneously wetted by water are called hydrophobic. Such membranes are obtained either from hydrophobic base materials, such as PP (polypropylene) or PTFE (poly tetrafluoroethylene), or by coating the pore surfaces with a hydrophobic layer, for example a perfluoro compound or a silane. The pore sizes of the membranes can also be adapted to the respective field of application, so that, on the one hand, sufficient separation of a fluid phase is ensured and, on the other hand, the pores are not blocked. The separation of the finest gas bubbles or liquid drops falls into the area of microfiltration. The pore sizes in microfiltration encompass an area that overlaps downward with ultrafiltration and upward overlaps with fine filtration. The pore sizes for microfiltration are usually between 0.1 μm and 10 μm. The selection of the pore fineness in the context of the invention depends both on the availability and compatibility of the materials and on the desired operating conditions. The more the pores are chosen, the finer the gas bubbles or liquid droplets can be separated, but at the same time the permeability of the membrane generally decreases. This can be a limiting factor, particularly for membranes that allow liquid to permeate. This effect can be compensated for by larger membrane areas. Typical pore sizes, which prove to be suitable in the area of microdialysis, are e.g. B. in the range of 0.1 microns to 0.5 microns.

The device according to the invention can also be used to additionally carry out sterile filtration of the fluid, as will be explained in more detail below. Membranes with a pore size of 0.45 or 0.22 μm have proven to be advantageous for this. In an advantageous embodiment, microfiltration hollow fiber membranes are used as membranes, wherein the hydrophobic and / or hydrophilic membrane can be designed in the form of a hollow fiber membrane. If both the hydrophilic and the hydrophobic membrane are used in the form of a hollow fiber, the membranes are arranged one inside the other so that, for. B. in one

Device for gas separation, the hydrophilic microfiltration membrane is at least partially inserted within a region of the hydrophobic microfiltration membrane, the respective end of the membranes being fluidically sealed with the supply and discharge lines by adhesive bonding. In the example described, the hydrophilic microfiltration hollow fiber membrane thus has an outside diameter which is smaller than the inside diameter of the hydrophobic microfiltration membrane.

The device according to the invention is of simple construction and can also be easily produced on a microscale using commercially available components. For example, a commercially available PTFE hollow fiber membrane (poly-tetra-fluoro-ethylene) is used for this. The outer diameter of 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 of approximately 0.45 mm, which is correspondingly smaller than that of the hydrophobic membrane, and an inner diameter which is reduced by approximately 0.1 mm. Such membranes, as described for. B. from Gore in Munich or Memtec Corp. Australia delivered. For example, silicone hoses, in which the membrane is integrated as described, are used as the inlet and outlet of the device. Of course, the supply and / or discharge of the device can also be formed entirely by the hollow fiber membrane, so that no additional elements are provided for the supply and discharge. 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 are each directly fluidly connected to the tubes of the microdialysis system, for example using a two-component adhesive. In a device as described, the hydrophilic membrane is then inserted into the end of the hydrophobic membrane after the adhesive has hardened. The end of the hydrophobic membrane is then also glued 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 a disposable unit if necessary.

If the device is used in the field of microdialysis, care should also be taken when selecting the materials that are used to manufacture the systems that the material is compatible with the dialysate or microperfusate and that there are no changes in the concentration of the analyte to be determined or influence the analysis as such unpredictably.

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

Should the application of the device also for much higher

Flow velocities are suitable, in an advantageous embodiment, the flow velocity in the area of the membranes can first be slowed down. If the length and / or the diameter of the membranes used is increased to such an extent that there is a reduction in the flow rate, and thus a sufficiently long residence time of the fluid in the exchange area is ensured, the phase separation is thereby supported.

In a preferred embodiment, a microfluidic flow system with a device according to the invention further includes a pump, by means of which the flow rate of the liquid is controlled. In this way, in addition to an influence on the phase separation, an exact determination of the amount of liquid flowing through is also possible. B. proves necessary especially when measuring analysis concentrations. If a device as described is used for gas separation in the area of the microdialysis and the device is installed in the flow direction upstream of the pump, it is ensured that no gas bubbles are conveyed which would falsify a measured volume of liquid. Based on an exact volume determination of the transported dialysate, an exact glucose concentration can now be calculated. In addition, the system can preferably be operated independently of the position, so that the device is also suitable for everyday use in the field of continuous diagnostics. In order to ensure that the device can be operated in any position, the feed line has a corresponding membrane system essentially in all spatial directions. The phase to be separated can then escape from the feed line through the membrane or the membrane system regardless of the position of the device and the density of the phase to be separated.

Experiments with the systems described consequently show that the system according to the invention, despite the simple structure, allows an essentially complete separation of two phases of a fluid and the operating conditions e.g. B. in a microdialysis system is sufficient.

For use in the field of microdialysis, the system is also 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. As already described, the system of microanalysis serves 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 as. B. glucose, lactate, proteins, minerals and neurotransmitters. In the context of the present invention, the term “body fluid” can encompass all possible body fluids such as in particular interstitial fluid, blood and brain fluid. The system is primarily designed for continuous diagnostics in humans, but other possible applications, e.g. B. on the animal to be included. In the context of the present invention, the term microdialysis system is used for an embodiment in which there is a membrane exchange between the exterior and a perfusion fluid. Milαodialysis systems which are known in the prior art are described, for example, in documents EP 0 649 628 and US Pat. No. 5,174,291. However, the device is suitable for. B. also for processes that are generally referred to as ultrafiltration. Filtration of the body fluid surrounding the system is first achieved through a membrane in the ultrafiltration system. The purpose of the ultrafiltration membrane is primarily 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 the process of ultrafiltration by way of example. The exchange area in which the membrane of the ultrafiltration system is present preferably has an elongated shape so that it has the shape of a rod. The end of the rod can be pointed, for example, so that an introduction into the human body is facilitated. A large number of different types of application sets exist in the prior art, which are not dealt with in more detail at this point. It is merely representative of the 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 z. B. a metal electrode can be used, which is coated on its surface with glucose oxidase or a reagent mixture containing glucose oxidase. However, for example, dissolved glucose oxidase can also be added to the measuring cell. This measurement method is e.g. B. described in document EP B 0 393 054. Bubble-free transport of the liquid is described as an essential aspect for an exact detection of the analyte concentration, so that there is no gas at the electrodes, which would lead to undefined states.

Furthermore, when performing a microdialysis, it is advantageous to provide a reservoir for perfusion liquid and / or a reservoir for holding dialysate after the analysis, which reservoir is connected to the exchange area directly or via a channel. A pump is provided to transport perfusion fluid through the exchange area and to the sensor area. Such a pump can, for example, operate in pressure mode and thus push liquid out of the reservoir for perfusion liquid, or it can also operate in suction mode and draw liquid through the system. Furthermore, a pump can, for example, be arranged such that it draws liquid out of the fluid reservoir and supplies it to the exchange area. The latter variant can be designed analogously to a conventional peristaltic pump, in which liquid is displaced by a roller element acting from the outside by squeezing together a compressible region of the fluid channel. Appropriate

Systems, for example, are used in the area of "implanted delivery devices". As an example, reference is made to document WO99 / 41606 from the field of microdialysis. The prior art shows that, for example, channels with a diameter in the range of 10-1000 μm are used in microdialysis, resulting in a channel length in the range of a few centimeters. For a linear flow rate of approximately 1 cm / min, pressures in the range of a few millibars have proven to be sufficient. Furthermore, such systems have an evaluation unit connected to the sensor, which are used to convert sensor signals into concentration values of the analyte.

For the device for separating liquid from a gas, a variety of applications are also conceivable, such as. B. in the field of medical technology. For example, there is an application in the field of artificial ventilation, where the device for removing liquid drops from a humidified gas stream can be used. Further areas of application are e.g. B. Analysis systems used to analyze the air we breathe.

Especially in the field of application of analysis it can be seen that measurement errors often occur which are caused by liquid drops in the gas analyzer. These arise e.g. in which the gas exhaled by humans in

Analysis system experiences a cooling from body temperature. Upon contact with the analysis system, the water contained in the breathing air is condensed out. A device according to the invention makes it possible, for example, to separate water in liquid form from the breathing air before it is passed into a CO analysis device. If the device - as described - is used for liquid separation, it proves to be advantageous to wet the liquid-permeable membrane first with liquid before using the device, so that no gas can escape through the dry membrane at the start of the measurement. An exact analysis of a gas flow is thus guaranteed during the entire measurement process.

In addition, there are further areas of application in analysis and in the synthesis of high-purity substances, each of which is carried out on a microscale, so that the devices according to the invention are generally not restricted to any specific area of application.

In principle, complementary uses are also conceivable for the application areas described, so that, for. B. a device according to the invention can also be used for gassing a liquid. Experiments have shown that in the case of a previously degassed solution which flows through the device according to the invention at a flow rate of 1.2 μl / min, comparable gassing of the liquid can be achieved, as is achieved in a conventional way by gassing with a silicone hose of the same diameter.

The system according to the invention can preferably be operated at normal pressure, the usual fluctuations in the ambient pressure essentially not impairing the separation of the phase to be separated.

The device according to the invention is furthermore not limited to a predetermined application time in a system, since the phase to be separated is always derived by the feed line. Nevertheless, care must be taken to ensure that the device is always functional. Here it is u. a. it is conceivable that the membrane may become dirty and thus the pores may become blocked, which impair the functionality of the device; especially if the device also serves, in addition to the gas or liquid separation function according to the invention, to separate particles within the fluid. Particles that are larger than the pore diameter are retained in the feed line of the system, so that the fluid passes the discharge line essentially without particles. For example, the device can be used to separate microorganisms from a fluid. Under these circumstances, the device is also used for the sterilization of fluids. Such an additional function of the device can, however, lead to the above-described contamination, in particular of the membrane of the discharge line, so that the service life of the device may be limited depending on the field of application. In order to ensure the functionality of the device, in an advantageous embodiment a sensor is integrated in the microfluidic flow system, which measures the fluid after the phase separation step. Such a sensor is e.g. B. within the derivative or generally downstream with respect to the device according to the invention within the system, and z. B. can be realized in a microdialysis probe. For example, the sensor is then used to detect bubbles or liquid drops in the fluid or to detect the

Flow rate that would drop accordingly if the membranes became blocked. If a sensor monitors the function of 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 article and can be used in the system intended for use can be easily exchanged. Of course, it is also conceivable to clean the device again if the membrane is contaminated by appropriate rinsing processes. With regard to the simple and inexpensive manufacture of the device, however, the use of the system as a disposable item proves to be preferred.

The subject of the invention is explained in more detail below with reference to the figures.

Figure 1: Device for gas separation with supply and discharge in the form of a hollow fiber membrane.

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

Figure 1 shows a device (10) for gas separation, which is integrated in a hose system (1). The hose system (1) is fluidly connected to the device (10) for gas separation and is connected to the device via an adhesive (5). The adhesive (5) is selected so that it seals the system fluidically and is consequently impermeable to the fluid (4) to be transported within the system. The device (10) has a feed line (2) which, in the example shown, is formed entirely by a hydrophobic hollow fiber membrane. The derivation (3), which is likewise completely formed by a hydrophilic hollow fiber membrane, is guided within the hydrophobic hollow fiber membrane. If liquid passes the area of the hose system in which the device for gas separation is integrated and gas is contained in the liquid, the liquid is separated from the gas phase in the area of the hydrophilic membrane. Here, only the fluid in the liquid state can pass through the hydrophilic membrane and thus reach the hose area (lb). The bubbles (6) contained in the liquid consequently accumulate in the feed line in front of the hydrophilic membrane, where they can escape through the hydrophobic membrane of the feed line (2). The hydrophobic membrane extends into all of them

Spatial directions, so that the gas bubbles can escape regardless of the bearing of the device.

FIG. 2 shows a further device for gas separation according to the invention. The device has a feed line (2) which has a hydrophobic membrane (2a) in a front area. The supply line is fluid with the discharge line (3) connected, which is closed at the front end by a hydrophilic membrane (3a). If liquid (4) is transported from the supply line to the discharge line, this must pass through the hydrophilic membrane (3a) positioned at the front end of the discharge line (3), which extends in the form of a separating layer through the hose system and thus the supply line from the discharge line separates. The hydrophilic membrane (3a) is preferably glued or welded to the discharge line (3) by a polymeric material (5). It is at a distance from the hydrophobic membrane (2a) which is preferably between 0 and a maximum of 10 times, preferably 2 times, in particular 0.5 times the diameter of the inlet or outlet. Gas bubbles that collect within the liquid in the front area of the feed line can escape through the hydrophobic membrane (2a), analogously to FIG. 1, so that the liquid (4) is degassed.

The embodiments shown are to be understood as examples and can be varied in many ways within the scope of the invention. According to the invention, a combined arrangement of a hydrophobic and hydrophilic membrane allows phase separation for microfluidic systems.

Claims

claims

1.Microfluidic device for gas separation from a microfluidic flow-through system comprising - a fluidic feed line which has a hydrophobic membrane at least in one area, through which gas can escape in the feed line, and a drain line which has a hydrophilic membrane in at least one area, which is essentially permeable to a liquid and impermeable to a gas, the supply and discharge lines being fluidly connected to one another in such a way that a liquid which flows from the supply line into the discharge line must pass through the hydrophilic membrane.

2.Microfluidic device for liquid separation from a microfluidic flow system, comprising a fluidic feed line, which has a hydrophilic membrane in at least one area, through which liquid can escape in the feed line, and a drain line, which has a hydrophobic membrane in at least one area is essentially permeable to a gas and impermeable to a liquid, the supply and discharge lines being fluidly connected to one another in such a way that a gas which flows from the supply line into the discharge line must pass through the hydrophobic membrane.

3. Apparatus according to claim 1 or 2, wherein the feed line has one or more membranes essentially in all spatial directions.

4. The device according to claim 1 or 2, wherein the hydrophobic membrane is a hollow fiber membrane.

5. The device of claim 1, 2 or 4, wherein the hydrophilic membrane is a hollow fiber membrane.

6. The device according to claim 1, in which the hydrophilic membrane is arranged within a region of the hydrophobic membrane.

7. The device of claim 2, wherein the hydrophobic membrane is disposed within a region of the hydrophilic membrane.

8. The device according to claim 1 or 2, wherein the hydrophobic and hydrophilic membrane are arranged in close proximity to one another and the distance of the membrane to each other is smaller than 10 times the diameter of the feed or discharge lines.

9. The device according to claim 8, wherein the hydrophobic and hydrophilic membrane are arranged in close proximity to each other and the distance of the membrane from each other is less than 2 times, advantageously less than 0.5 times the diameter of the feed or discharge.

10. The device according to claim 1 or 2, which is integrated in a hose line.

11. The device according to claim 1 or 2, which is such that the flow rate of a fluid is reduced in the region of the membrane of the feed line.

12. The apparatus of claim 1 used in an ultrafiltration system.

13. The apparatus of claim 1 used in a microdialysis system.