EP1167757B1

EP1167757B1 - Pump for low flow rates

Info

Publication number: EP1167757B1
Application number: EP01114608A
Authority: EP
Inventors: Carlo Effenhauser; Herbert Harttig; Peter Kraemer
Original assignee: F Hoffmann La Roche AG; Roche Diagnostics GmbH
Current assignee: F Hoffmann La Roche AG; Roche Diagnostics GmbH
Priority date: 2000-06-21
Filing date: 2001-06-19
Publication date: 2004-10-06
Anticipated expiration: 2021-06-19
Also published as: US6860993B2; DE10029453C2; DE10029453A1; DE50103943D1; ES2228700T3; US20050006309A1; US6872315B2; US20020087110A1; AT278874T; EP1167757A3; EP1167757A2

Description

The present invention relates to a pump for flow rates in the range of about 1 to 1000 nl / min. In particular, pumps according to the invention are for applications in the medical field Diagnostics such as microdialysis or ultrafiltration are suitable.

What is claimed is a pump for low flow rates, which has a channel that at least is partially filled with a transport liquid and one that can be wetted by the transport liquid Membrane, which closes an opening of the channel and through which an evaporation can be done. Located on the side of the membrane opposite the transport liquid a room with a substantially constant vapor pressure of the transport liquid. to Invention also include microdialysis and ultrafiltration systems, with a pump like mentioned above.

Miniaturized pumps are known in the art e.g. Peristaltic pumps, with which flow rates down to about 100nl / min can be achieved. In the focus of development miniaturized pumps generally have the highest possible delivery rate with minimal Pump volume. It has also been shown that such pumps in long-term applications in lower conveyor range do not work reliably and in particular larger fluctuations of the flow rates achieved can hardly be avoided. In the field of ultrafiltration and microdialysis Arrangements are also known in which a vacuum reservoir (for example a drawn-up syringe) connected to a fluid system via a capillary throttle section is. The disadvantage here is the non-linear pressure curve over time. Another Arrangement for achieving low flow rates is known from document WO 95/10221. at This arrangement becomes a liquid in a channel with a sorbent brought into direct contact. Such a system typically has flow rates in the range of a few µl / min. The long-term constancy (measured over several days) of this pump is fair low.

The object of the present invention was to provide a pump for very low flow rates to provide, which works reliably and a sufficiently high constancy of the flow rate, over has a longer period (e.g. several days). Furthermore, it was the task of the present Invention to propose a pump for such low flow rates that is very simple and is inexpensive to manufacture. The pump should also be easy to manufacture with integrated microfluidic systems based on planar technologies (e.g. micro technology) compatible his.

In a pump according to the invention there is a transport liquid in a channel which has an opening which is closed by a membrane wettable by the transport liquid is. Due to capillary effects, transport liquid enters the membrane and is essentially through capillary channels through the membrane into a gas space constant vapor pressure of the transport liquid removed, or from a suitable sorbent physically or chemically bound (absorbed) so that further evaporation can take place freely through the membrane. The constant vapor pressure conditions cause a constant flow rate in the gas space.

In the context of the invention, transport fluids can generally be used, which in penetrate a membrane and evaporate through it. Are preferred within the scope of the present Invention aqueous transport liquids. In addition to the water content, aqueous Transport fluids contain substances or mixtures of substances that affect the surface tension and / or influence the viscosity, so the penetration behavior of the transport liquid into the To be able to adjust the membrane to a desired value. The transport liquids preferably contain however no substances that cannot be evaporated at room temperature, such as e.g. B. Salts as these could clog the membrane. For cases where liquids to be transported with non-evaporable substances are also below suitable embodiments are described.

The channel of the pump according to the invention preferably has an area in the range from 1 to 10 ⁵ μm ² and a length of 1-1000 mm. In the area of the wettable membrane, the cross section is preferably enlarged laterally (1 to 1000 mm ² ) in order to provide a sufficiently large exchange surface with the adjacent gas space. The evaporation process on the membrane removes transport liquid from the fluid channel, so that a negative pressure is generated which produces the desired pumping action. The pump can be used to transport the transport liquid itself if it is used, for example, as a perfusion liquid in the context of a microdialysis. In another embodiment according to the invention, a working fluid which is used, for example, as a perfusate or else for other purposes is located in the fluid channel, segmented by the transport liquid. In another application of the pump, for example ultrafiltration, evaporation of the transport liquid creates a negative pressure in the channel, which transports a fluid from the environment into the fluid channel. In the field of ultrafiltration, this would be an external fluid (interstitial fluid) that enters the channel through an ultrafiltration membrane.

The term membrane in the sense of the present invention is intended to generally include structures is sucked and evaporated by the liquid through capillary forces from the fluid channel. In addition to the bodies commonly referred to as membranes, the one Arrays also have a large number of generally disordered capillary channels (Under certain circumstances only a few) capillary channels can be covered by the term membrane. A Such an embodiment is described in more detail in connection with the figures. Such Capillary arrays can be manufactured using microtechnical methods, with very small ones and constant cross sections can also be achieved. With such capillary-active membranes can be realized very low flow rates, the manufacturing technology on the number and Cross-section of the capillary channels can be adjusted.

By sealing with a hydrophobic, non-wettable membrane (e.g. Teflon) the Evaporation rate can also be checked.

In cases where either direct contact of the liquid to be transported with the Evaporator membrane must be avoided, such as. B. in the case of transport salty Liquids in which the immediate evaporation at the membrane to form a solid salt residue with a corresponding harmful effect on the constancy of the evaporation rate would lead, or for example if for the liquid to be transported no suitable sorbent is available, the detour can be made via an additional one Transport liquid (e.g. degassed and deionized water) the function of the Ensure the pump.

In the case of liquids that are not miscible with each other (e.g. toluene to be transported Liquid (working fluid), water as evaporating transport liquid), it is possible that both liquids are present directly in the system with a common phase boundary without the liquid to be transported during a prolonged pumping operation (e.g. over several days) can come into contact with the membrane. This can be done by a Stock of transport liquid can be reached in an intermediate buffer, which is preferably larger than the total volume of liquid to be transported (working fluid).

In the case of miscible liquids, the two liquids (e.g. Ringer's solution and pure water) can be segmented from each other via an impermeable membrane. Prefers In this case, a diffusion barrier can also be used, in which the above-mentioned Example the Ringer's solution one or more interconnected reservoirs (i.e., a dilution cascade) displaced water volume and the associated dilution ensures a sufficient reduction in the salt concentration on the evaporation membrane. Salting out of the membrane, which can change the pumping rate, can occur Consequences would have to be avoided or at least reduced. The advantage of this solution is that Avoid moving parts (e.g. a sagging membrane) and in the simple manufacture and integration into the pump body.

Another advantage of this solution is that the reservoirs depend on the geometric design of the transport route in whole or in part as a bubble trap for possible in the to be transported Gases present in the liquid or released during transport can act and so one Help prevent direct contact of gas bubbles with the evaporation membrane.

Another easy way to segment liquid and liquid to be transported Transport liquid consists in introducing a gas bubble that both liquids permanently separates from each other. The volume of this gas bubble must be large enough to to guarantee segmentation for all changes in cross-section of the transport route, if necessary also in the container that serves as a storage medium for the transport liquid.

An advantage of the solution with one or more reservoirs for the dilution of the transported Liquid versus gas bubble for segmentation is that even after stronger shaking movements, which in the case of gas bubble segmentation to mix the Could carry liquids, the function is still guaranteed. A possible resolution the gas bubble in the liquid also has the disadvantage of an additional temperature dependence the flow rate due to temperature-related expansion / contraction of the gas buffer on.

An essential aspect of the present invention is that which can be wetted by the transport liquid Membrane. The pumping effect of the membrane is based on the fact that there is a liquid is sucked up by surface forces in capillaries or pores of the membrane. The one on this Capillary pressure that can be generated in this way is directly proportional to the surface tension of the liquid and the cosine of the contact angle of the liquid with the membrane material and vice versa proportional to the radius of the capillaries or pores. Within the scope of the present invention membranes are therefore suitable, the contact angle of which on the part of the transport fluid is between 0 and 90 degrees. From the given context it can also be seen that the capillary pressure increases with decreasing diameter of the capillaries or pores. typical Pore diameters of capillaries in the membrane are in the range from 10nm to 100µm. It is important for the present invention that the transport liquid is in direct contact occurs with the membrane so that a capillary effect occurs. Accordingly, must be prevented be that the liquid contact between the transport fluid and membrane breaks off, which is the case can be when the pore diameter of the membrane becomes too large and thereby the capillary pressure decreases, or also be caused by a defect (hole) in the membrane can, which leads to a pressure compensation by back-flowing gas.

In the context of the invention, it is also advantageous to use membrane systems that in addition a wettable membrane have another membrane on which the transport liquid facing away from the first membrane. For this second membrane you can such membranes are used, in which no liquid with high surface tension can penetrate, for example membranes made of PTFE, Cuprophan ® or Gambran ®. About the Properties of this second membrane can reduce the evaporation rate of the transport liquid be modulated. Furthermore, membranes can be used, the different Have areas of which an area facing the transport liquid is wettable and a remote area is not wettable.

Integrated manufacture of pump body and diaphragm (monolithic) is also possible or the use of customized membranes with a defined pore size and distribution in a hybrid approach. The integrated manufacture of such membranes is e.g. B. based on silicon described in T. A. Desai et al, Biomedical Microdevices 2 (1999), 11-41. Another possibility is to use a microporous Si membrane with statistical Distribution of pore sizes (R.W. Tjerkstra et al., Micro Total Analyors Systems '98, Kluwer 1998, pp. 133-136). In polymer substrates such membranes can e.g. B. with Laser ablation, hot stamping, etc. can be produced.

The pumping action of the membrane used is maintained as long as the partial pressure the liquid to be pumped on the side of the membrane facing away from the liquid (gas side) is less than the saturation vapor pressure at the respective working temperature. To the Keeping vapor pressure constant (and minimizing any environmental impact) is suggested to provide a gas space containing a sorbent which is not in direct contact to the wettable membrane. Due to the constant sorption of the vaporized liquid becomes a constant difference in vapor pressure across the liquid in the pores and the Saturation vapor pressure maintained.

The term sorbent is intended to include both adsorbent and absorbent. As Sorbents are, for example, silica gels, molecular sieves, aluminum oxides, Ceolithe, Clays, activated carbon, sodium sulfate, phosphorus pentoxide, etc. are suitable.

For the desired functioning of the pump, it is important that between the sorbent and there is no direct contact with the capillaries / pores of the wettable membrane, to avoid that liquid is transferred directly in this way. It is rather for Achieving low, long-term constant flow rates requires that vaporization first of transport liquid and the evaporated transport liquid from the gas phase is absorbed by the sorbent. This can be achieved by using the wettable Membrane and the sorbent are spaced apart and thus no direct Have fluid contact. It is also possible to use one (or more) non-wettable To use membrane, which is preferably arranged directly on the wettable membrane. The sorbent can also have direct contact with such a membrane, without creating a fluidic short circuit. With such an arrangement it is also possible to use a liquid sorbent, e.g. a highly concentrated or saturated saline solution use. Another option is to place the wettable membrane in one of the transport liquids to modify the area facing away or facing the sorbent, that the membrane is not wettable and thus the function of a second non-wettable Membrane takes over. Such a modification of the membrane can, for example can be achieved by a plasma reaction. In embodiments with membranes, the one have a wettable area and a non-wettable area, the sorbent Contact the non-wettable area directly without creating a fluid short circuit.

So that the sorbent can develop its function, it should be in a vessel (container) be arranged, which closes it from the outside and in particular penetration of Moisture from outside is largely prevented. The vessel has an opening that is closed by the wettable membrane or the non-wettable membrane. Consequently Vaporized transport fluid penetrates into the vessel through the membrane and becomes there by the sorbent added. The sorbent should be chosen so that the resulting Equilibrium vapor pressure of the transport liquid, which is lower than the saturation vapor pressure of the fluid is in the gas phase, above which the sorbent is constant for a long time. This is important to set a defined evaporation rate of the transport liquid, which the Flow rate constancy increased.

Surprisingly, it was found that in embodiments of the vessel in which the Sorbent with flexible walls has no negative impact on the pumping action on the contrary, that flow fluctuations caused by pressure changes in the outside or caused by temperature changes were significantly reduced. As flexible walls are especially foils, e.g. 3E aluminum composite films with low density and low bag strength. Elastic plastics, such as B. Silicones.

Surprisingly, it was found that a further, simplified embodiment, the completely without sorbent, also leads to very constant delivery rates. at this embodiment is above the side facing away from the transport liquid Membrane or the membrane composite through walls that form a housing a room enclosed, the walls having omissions between 0.001% and 100% the surface of the walls, i.e. in extreme cases, the housing is dispensed with. By the geometric dimensions of the omission and its frequency and the selection The gas permeable membranes can transport liquid vapor into the surrounding area Gas phase can be set over a wide range. There are also embodiments possible in which the side of the membrane opposite the transport liquid arranged space is not surrounded by a housing belonging to the pump. This is the case if the room has an essentially constant vapor pressure of the transport liquid has, as is the case with air-conditioned rooms. In particular, there are also configurations possible, in which the pump according to the invention within an air-conditioned Systems - for example an analyzer - is used.

The transport rate depends on a number of factors, of which the above Viscosity of the liquid and the membrane properties were mentioned. These influencing factors in turn depend on the temperature. For example, the temperature rises with increasing temperature Evaporation rate and also the rate of diffusion in the gas phase. In opposite In contrast, increasing temperature affects the viscosity of the liquid, the surface tension of the liquid and the interfacial tension between the membrane and the liquid. This results in a complex relationship between the transport rate and the temperature. By appropriate selection of the relevant materials, such as the membrane (s) and the sorbent However, it can be ensured that the temperature dependence is low. The present The invention is particularly suitable for applications under thermostatic conditions. On the one hand, active thermostatting can be carried out, for example, by with a Peltier element the temperature in the surrounding area of the membrane to one preselected range. An inventive one can be particularly advantageous Pump can be used in close contact with the human body. This is a direct one Contact of the housing in which the pump is located with the body surface is an advantage. Temperature control can also be supported by the pump or a microdialysis or ultrafiltration system thermally insulated on the sides that do not touch the body becomes. Furthermore, a temperature measuring unit can also be used in a system with a pump according to the invention be integrated, which reports deviations from a target temperature range or but also takes into account a currently measured temperature when evaluating analytical measured values.

In the delivery state, the pump according to the invention preferably has no direct one Contact of transport fluid and wettable membrane to an unnecessary consumption of To avoid liquid. The contact can by the user through a targeted pressure surge Commissioning of the pump can be generated.

Microdialysis and ultrafiltration systems can be used very advantageously with the liquid pumps according to the invention being constructed. The transport liquid can be used directly for microdialysis used as perfusate which is passed through a microdialysis catheter to take up analyte. Alternatively, it is possible to use a different one from the transport liquid Provide liquid (e.g. Ringer's solution) that is fluidly coupled to the transport liquid is.

With ultrafiltration, the consumption of transport liquid can be caused by the evaporation process used to create a negative pressure in the canal, the body fluid (interstitial Liquid) into an ultrafiltration catheter. Both in microdialysis and Ultrafiltration can also be downstream of the microdialysis membrane or ultrafiltration membrane a sensor for detecting one or more analytes can be provided.

Figur 1:: Querschnitt durch eine erste Ausführungsform einer Pumpe mit Sorptionsmittel
Figur 2:: Aufsicht und Querschnitt durch eine Pumpe gemäß einer zweiten Ausführungsform
Figur 3:: Flußrate einer Pumpe gemäß Fig. 1
Figur 4:: Querschnitt durch eine Pumpe ohne Sorptionsmittel
Figur 5:: Aufsicht und Querschnitt durch eine Verdünnungskaskade
Figur 6:: Querschnitt durch einen Membranbereich mit einzelnen Kapillaren

The present invention is explained in more detail with reference to figures:

Figure 1:: Cross section through a first embodiment of a pump with sorbent
Figure 2:: Top view and cross section through a pump according to a second embodiment
Figure 3:: Flow rate of a pump according to FIG. 1
Figure 4:: Cross section through a pump without sorbent
Figure 5:: Top view and cross section through a dilution cascade
Figure 6:: Cross section through a membrane area with individual capillaries

Figure 1 shows a cross section through a pump according to a first embodiment. The arrangement shown has a channel (2) with a diameter of 100 microns in which there is a transport liquid. In the case shown, water was used as the transport liquid selected. The channel is in an area of the transport channel with an enlarged cross section closed with a wettable membrane (4). In the present example it was used as a membrane a BTS 65 from Memtec (now: USF Filtration and Separations Group, San Diego, CA, USA) (PESu hydrophilized with hydroxypropyl cellulose). This highly hydrophilic Membrane is asymmetrical with pores in the range of 10 µm on one and 0.1 µm on the other Page. The side with larger pores faces the liquid. Above the wettable Membrane (4) is a non-wettable membrane made of expanded PTFE. The Non-wettable membrane is attached to the wettable membrane so that the transport liquid (3) facing away from the wettable membrane (4) is completely covered. Out The figure shows that the arrangement was chosen so that an evaporation of Transport liquid from the channel system can only take place via the wettable membrane (4). The system of wettable (4) and non-wettable membrane (5) is thus of a housing (7) surround that evaporated transport liquid only in the interior of the housing or vessel (7) can get. There is a sorbent inside the housing (7) (6), silica gel in the present example. (Molecular sieve MS 518, Grace Davison, Baltimore, Maryland, USA). From Figure 1 it can also be seen that the sorbent in direct There is contact with the non-wettable membrane. As described above, this is possible since the non-wettable membrane has a fluidic short circuit, i.e. H. a direct sorbing of liquid from the capillaries of the wettable membrane without a gaseous / vaporous Intermediate phase prevented. The pump shown experimentally became a flow rate achieved in the range of 1 to 1000 nl / min (nanoliters per minute) in the direction of the arrow (8).

FIG. 2 shows a system which is very economical in terms of production technology and can be miniaturized well. The The pump according to FIG. 2 has a base plate (9) with depressions that work together form a capillary system (11) with a cover (10). It can be seen from FIG. 2B how Base plate and lid are arranged to each other. Located between these two units there is a wettable membrane (12) which is arranged above a channel system (13). The The membrane can be attached by simply clamping it between the base plate and the cover. Lid and base plate can e.g. by gluing, pressing or ultrasonic welding be connected to each other. The channel system (13) can be easily in the bottom plate are formed by a recess in which there are additional webs that sag prevent the membrane. In this way, arise through cooperation with the membrane underside of capillary channels, which completely fill the channel system with Ensure transport fluid. With such a channel system, the surface is made of which occurs a transfer of transport liquid into the wettable membrane, enlarged. From figure 2B it can also be seen that the cover has a recess (14) which is above the Membrane (12) is arranged. Due to the relative arrangement of the channel, membrane and vessel Absorption of evaporated transport liquid ensures that the transport liquid can only exit into the recess (14). In the recess (14) that the vessel forms, there is a sorbent (15), the transport liquid located in the gas space (16) receives. The embodiment shown in Figure 2 comes with a single wettable Membrane (12). There is no need for a non-wettable membrane because Membrane and sorbent are spaced apart and only in the gas space in Exchange.

FIG. 3 shows a measurement of flow rates as achieved with an apparatus according to FIG. 1 were over a 6 day period. The measurement of the flow rate was by gravimetric Detection of the liquid taken in the reservoir made. The pump that too had the results shown in Figure 3, had a circular exchange surface the transport liquid with the membrane (diameter 2 mm). It became hydrophilic Membrane with the designation BTS 65 (see description above) and a non-wettable Polytetrafluoroethylene membrane used as an evaporation limiter. As a sorbent for the transport liquid (water) was used 8g silica gel. Aside from the advanced Part of the channel below the membrane had a diameter of 100 microns and a length of 40 cm. It can be seen from FIG. 3 that the flow rate in the period from 6 days only decreased from 100 nl / min to about 80 nl / min. For applications in the area of Microdialysis and ultrafiltration can tolerate such a change in flow rate as it does has no significant impact on the analysis result.

FIG. 4 shows a pump according to the invention without a sorbent. Regarding the Dimensions, as well as the wettable (4) and the non-wettable membrane (5) corresponds to this Pump that shown in Figure 1. A housing is located above the non-wettable membrane (7 '), which is arranged so that transport liquid (3) only in the space (16) of this housing is evaporated into it. The housing (7 ') differs from that shown in Fig. 1 Housing in that it has openings (17) on the evaporated transport liquid can escape from the room (16). Membranes can be provided instead of omissions, which allow diffusion of gaseous transport liquid. So for example it is possible to form the housing completely and without recesses from one material, that allows sufficient diffusion. Through the above-mentioned embodiments a diffusion equilibrium is achieved between the interior (16) and the surroundings, this ensures that the vapor pressure of the transport liquid in the interior (16) essentially is constant. This results in a largely constant evaporation rate and thus also achieved transport rate in channel (2).

Figure 5 shows a top view and in cross section of a dilution cascade as used can be sufficient to separate transport fluid and working fluid so that a Change in the evaporation rate on the membrane due to non-evaporable components (e.g. Salts) in the working fluid can be avoided. The dilution cascade shown (20) has a base body (21) which, for example, can be made of plastic and in case shown 8 has reservoirs. The reservoirs are through through holes formed in the base body (21), which are closed by cover plates (23, 23 '). On microstructured channels (24) are also provided in the base body, which after covering of the base body with the cover plates a fluid exchange between the individual Reservoirs and an inlet and outlet of liquid into the dilution cascade or from the dilution cascade.

The operation of the dilution cascade (20) shown is as follows:
The dilution cascade (20) is connected at its inlet opening (26) to a fluid system in which liquid is to be transported. With its outlet opening (27), the dilution cascade is connected to a pump according to the invention. When commissioning, the dilution cascade is filled with an evaporable liquid that contains no or only minor additions of non-evaporable components. Due to the action of a pump according to the invention, the liquid contained in the dilution cascade is now pulled out of the outlet opening (27) and the liquid to be pumped flows in at the inlet opening (26). The first reservoir (22 ¹ ) now mixes the liquid to be pumped with the dilution fluid contained in the dilution cascade. The further reservoirs (22 ² , 22 ³ , 22 ⁴ ...) are used for successive dilutions, so that, at the outlet opening (27) of the dilution cascade, virtually only dilution fluid emerges without substantial additions of the fluid to be transported. In order to ensure adequate functioning of the dilution cascade, the total volume pumped by the pump should be less than half, preferably less than a quarter, of the total volume of the dilution liquid in the dilution cascade

FIG. 6 shows the diaphragm area of a pump based on capillary channels produced using microtechnology. The fluid channel (2) branches into several capillaries (30) with a defined "pore diameter" and thus forms a membrane with a small number of pores. The end of one Capillary can be viewed as a single pore from which evaporation into the Gas phase takes place. The evaporation rate from the menisci in the capillaries can by a non-wettable hydrophobic membrane can also be regulated.

FIG. 6 shows a cavity (32) into which evaporation takes place from the capillaries. The cavity is closed off from the outside space by a membrane (31) to ensure substantially constant vapor pressure of the fluid in the cavity.

Claims

Pump for low flow rates comprising

a channel which is at least partially filled with a transport liquid (3) characterized in that the pump additionally comprises

a membrane (4, 12) at one opening of the channel that can be wetted by the transport liquid,

a space having an essentially constant vapour pressure of the transport liquid located at the side of the membrane opposite to the transport liquid such that the transport liquid is evaporated through the membrane.
Pump as claimed in claim 1, in which the space contains a sorbent (6, 15) which sorbs evaporated transport fluid.
Pump as claimed in claim 1, in which the space and the transport liquid are separated from one another by the membrane.
Pump as claimed in claim 2 or 3, in which the sorbent is located in a housing (7) having an opening, wherein the opening is closed by the membrane.
Pump as claimed in claim 3 or 4, in which the sorbent has no direct contact with the membrane.
Pump as claimed in claim 1, in which the space is formed by a housing (7') which exchanges evaporated transport liquid with the outer space.
Pump as claimed in claim 1, in which the membrane is hydrophilic.
Pump as claimed in claim 1, in which the membrane has a hydrophilic region facing the transport liquid and a hydrophobic region which faces the sorbent.
Pump as claimed in claim 8, in which the sorbent is in contact with the hydrophobic region of the membrane.
Pump as claimed in claim 1, which has at least one non-wettable membrane (5) which is located on a side of the wettable membrane facing away from the transport liquid.
Pump as claimed in claim 1, in which the channel contains a working liquid that is segmented from the transport liquid.
Pump as claimed in claim 1, in which the membrane is formed by an array of capillary channels.
Pump as claimed in claim 12, in which the capillary channels are located in a body in which the channel conveying the transport liquid is also located.
Pump as claimed in claim 12 or 13, in which the capillary channels are manufactured by microtechnology using etching processes, laser machining, or by stamping, injection moulding or moulding processes.
Pump as claimed in claim 12, in which the array comprises 3 to 100, preferably 5 to 25 capillary channels.
Pump as claimed in claim 12, in which the capillary channels of the array have a diameter of the individual channels in the range of 10 nm to 100 µm.
Microdialysis system comprising a pump as claimed in claim 1 and a microdialysis membrane past which the transport liquid or a working liquid is transported by the pump.
Microdialysis system as claimed in claim 17 containing a sensor located downstream of the microdialysis membrane for the detection of one or several analytes in the transport or working liquid.
Ultrafiltration device comprising a pump as claimed in claim 1 and an ultrafiltration membrane through which the body fluid is drawn into the channel.
Ultrafiltration device as claimed in claim 19 containing a sensor located downstream of the ultrafiltration membrane for the detection of one or more analytes in the body fluid.
System for pumping a working liquid at a low flow rate, wherein at least one dilution reservoir (22) containing a liquid which is essentially free of substances that cannot evaporate at the membrane is located between the fluid system in which the working liquid is located and a pump as claimed in claim 1.
System as claimed in claim 21, in which two or more reservoirs that are connected to one another (22¹, 22², 22³, 22⁴, 22⁵, 22⁶, 22⁷, 22⁸) which form a dilution cascade are arranged between the fluid system of the working liquid and the pump.