Sampling device and sampling method

Abstract

The present invention relates to a sampling device, a sampling system and a method of sampling, and in particular a method of analysis, for application to a living entity.

Claims

1. A sampling device for a sampling access to detect the presence of analyte in a sample, comprising: a sample chamber taking the form of an internal cavity enclosed within the sampling device, wherein the sample chamber includes a first opening in a first end of the sampling device, said first opening being a sample inlet to receive a sample and a second opening at a second end of the sampling device opposite said first end; an analyte receiving chamber enclosed within the sampling device and surrounding a portion of the sample chamber; a separating medium defining an interface between the sample chamber and the analyte receiving chamber, the separating medium adapted to allow the analyte to pass through from the sample chamber into the analyte receiving chamber; an infeed line passage extending from an infeed line passage opening in the second end of the sampling device to an analyte receiving chamber inlet opening; and an outfeed line passage extending from an analyte receiving chamber outlet opening to an outfeed line passage opening in the second end of the sampling device, wherein said sampling device is adapted so that fluid fed into the infeed line passage opening flows into a first end of the analyte receiving chamber, then along the length of the analyte receiving chamber to a second end of the analyte receiving chamber, before flowing into the outfeed line passage and exiting through the outfeed line passage opening.

2. The sampling device of claim 1, wherein a cross-section of the sampling device where the analyte receiving chamber surrounds the sample chamber includes a ring-shaped analyte receiving chamber surrounding a circular sample chamber separated by a ring-shaped separating medium.

3. The sampling device of claim 1, wherein the first end of the analyte receiving chamber is located at the second end of the sampling device and the second end of the analyte receiving chamber is located at the first end of the sampling device.

4. The sampling device of claim 1, wherein at least one of: the sample chamber takes the form of a passage extending through the sampling device the sampling device is designed for fitting to a medical sampling access that includes at least one of a hollow needle, a cannula, a catheter, a port, an aspirator, a drain, a reservoir and a connector, and the sampling device is designed for connection by positive interengagement, a normal force and/or friction to the medical sampling access.

5. The sampling device of claim 1, wherein the sampling device is integrally connected to the sampling access.

6. The sampling device of claim 1, wherein at least one of: the sampling device is designed to receive the sample that is selected from at least one of blood, blood plasma, lymph, tissue fluid, cerebrospinal fluid, synovial fluid, gastric juice, gall and urine, and the separating medium is designed to allow the passage of the analyte selected from glucose, lactose, lactate, Na.sup.+, K.sup.+, Cl.sup., H.sub.3O.sup.+, O.sub.2, CO.sub.2, ammonium, ammonia, methanol, ethanol, formate, acetate, glutamine, glutamate, urea, uric acid, phosphate, antibodies, growth factors, hormones, medications, and narcotics and anesthetics.

7. The sampling device of claim 1, wherein the separating medium is a membrane and the material of the membrane is selected from the group comprising cellulose and derivatives thereof that include at least one of cellulose acetate, PTFE, polycarbonate, polypropylene, polyamides, polyesters, polyethersulfones and polysulfones.

8. The sampling device of claim 1, wherein at least one of: the inside diameter of the infeed-line passage and/or the outfeed-line passage, at the analyte receiving chamber, is from 0.01 to 2 mm, and the interface of the separating medium that connects the sample chamber to the analyte receiving chamber is has an area from 0.5 to 350 mm.sup.2.

9. The sampling device as claimed in claim 1, wherein at least one of: the inside diameter of the infeed-line passage and/or the outfeed-line passage, at the analyte receiving chamber, is from 0.25 to 0.5 mm, and/or the interface of the separating medium that connects the sample chamber to the analyte receiving chamber has an area from 1 to 50 mm.sup.2.

10. The sampling device as claimed in claim 1, wherein at least one of: the inside diameter of the infeed-line passage and/or the outfeed-line passage, at the analyte receiving chamber, is from 0.23 to 0.26 mm, and the interface of the separating medium that connects the sample chamber to the analyte receiving chamber has an area from 2 to 35 mm.sup.2.

11. The sampling device of claim 5, wherein the sampling access comprises at least one medical sampling access selected from the group consisting of a hollow needle, a cannula, a catheter, a port, an aspirator, a drain, a reservoir, and a connector.

12. A sampling system, comprising the sampling device of claim 1, a sensor connection for connecting a sensor for detecting analyte in a transporting medium, an infeed line, in fluid communication with the infeed-line passage of the sampling device, an outfeed line, in fluid communication with the outfeed-line passage of the sampling device and with the sensor connection, a first pump to transport a medium through the outfeed line to the sensor connection.

13. The sampling system of claim 12, further comprising: a supply of transporting medium and/or a supply of calibrating medium and/or a supply of flushing medium, that are/is in fluid communication, or can be placed in fluid communication, with the infeed line.

14. The sampling system of claim 13, wherein the first pump is arranged between (a) the supply of transporting medium and/or the supply of calibrating medium and/or the supply of flushing medium and (b) the infeed-line passage of the sampling device, to allow medium to be transported from the given supply of medium through the infeed line into the infeed-line passage, and further comprising a control system connected to the first pump, to control the latter in such a way that: Step a: transporting medium is present in the analyte receiving chamber for a preselected time and then Step b: transporting medium is transported from the analyte receiving chamber into the outfeed-line passage.

15. The sampling system of claim 12, further comprising a control system, connected to the second pump, to control the second pump in such a way that Step 1: the sample is drawn by suction into the sample chamber, Step 2: the sample that was drawn in is present in the sample chamber for a preselected time and then Step 3: the sample that was drawn in is expelled from the sample chamber, the control system being so arranged that the first pump is controlled in such a way that, in step 2: Step a): transporting medium is present in the analyte receiving chamber for a preselected time and then Step b): transporting medium is transported from the analyte receiving chamber into the outfeed-line passage.

16. The sampling system of claim 12, further comprising at least one of: in fluid communication with the sensor connection, a sensor arranged to determine an analyte selected from glucose, lactose, lactate, Na.sup.+, K.sup.+, Cl, H30.sup.+, O2, CO2, ammonium, ammonia, methanol, ethanol, formate, acetate, glutamine, glutamate, urea, uric acid, phosphate, antibodies, growth factors, hormones, medications, and narcotics and anesthetics, and the sampling system being designed to receive the sample selected from blood, blood plasma, lymph, tissue fluid, cerebrospinal fluid, synovial fluid, gastric juice, gall and urine, and the sampling system further comprising a bypass line for the placing in fluid communication of the supply of transporting medium and/or the supply of calibrating medium and/or the supply of flushing medium with the sensor connection, without the medium passing through the analyte receiving chamber of the sensor device.

17. The sampling system of claim 12, further comprising a sampling line and, connected thereto, a second pump for pumping the sample into the sample chamber.

18. A sampling device to detect the presence of analyte in a sample, comprising a hollow needle comprising: a sample chamber taking the form of an internal cavity enclosed within the hollow needle, wherein the sample chamber includes a first opening in a first end of the hollow needle, said first opening being a sample inlet to receive a sample and a second opening at a second end of the sampling device opposite said first end; an analyte receiving chamber enclosed within the hollow needle and surrounding a portion of the sample chamber; a separating medium defining an interface between the sample chamber and the analyte receiving chamber, the separating medium adapted to allow the analyte to pass through from the sample chamber into the analyte receiving chamber; an infeed line passage extending from an infeed line passage opening in the second end of the hollow needle to an analyte receiving chamber inlet opening; and an outfeed line passage extending from an analyte receiving chamber outlet opening to an outfeed line passage opening in the second end of the hollow needle, wherein said sampling device is adapted so that fluid fed into the infeed line passage opening flows into a first end of the analyte receiving chamber, then along the length of the analyte receiving chamber to a second end of the analyte receiving chamber, before flowing into the outfeed line passage and exiting through the outfeed line passage opening.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) In the drawings:

(2) FIG. 1 is a schematic view in cross-section of a sampling device comprising a window provided with a separating medium, by which the sample chamber and the analyte receiving chamber are connected together.

(3) FIG. 2 is a schematic view in cross-section of a sampling device as shown in FIG. 1 having spacers.

(4) FIG. 3 is a schematic view in cross-section of a sampling device as shown in FIG. 1 having a filter.

(5) FIG. 4 is a schematic view in cross-section of a sampling device according to the invention, with the analyte receiving chamber surrounding the sample chamber and the sample chamber taking the form of a passage extending through the sampling device.

(6) FIG. 5 is a schematic view of the exterior of a sampling device as shown in FIG. 4, when fitted with a Luer lock connector.

(7) FIG. 5a is a schematic view of a further sampling device as shown in FIG. 4 having a Luer lock connector.

(8) FIG. 6a is a schematic view of the exterior of a sampling device that is designed in the form of a probe.

(9) FIG. 6b is a schematic view of the use of sampling devices in conjunction with a sampling access in the form of a catheter.

(10) FIGS. 7a and 7b are schematic views of the use of a, sampling device according to the invention in conjunction with a sampling access in the form of a cannula.

(11) FIG. 8 is a schematic view of a sampling system according to the invention.

(12) FIG. 9 is a schematic view of an alternative to the sampling system shown in FIG. 8, for longer distances between the sampling device and the sensor.

(13) FIG. 10 is a schematic view of a further alternative to the sampling system according to the invention shown in FIG. 8, having an alternative outlet.

(14) FIGS. 11a and 11b are schematic views of a further alternative to the sampling system according to the invention shown in FIG. 8, having alternative fluid storage and infeed-line systems.

(15) FIG. 12 is a schematic view of a further, very compact, alternative to the sampling system according to the invention shown in FIG. 8.

(16) FIGS. 13a and 13b are schematic views of a sampling device according to the invention serving a plurality of patients or having a plurality of sensors or measuring stations.

(17) FIG. 14 is a schematic view of a catheter having an inflatable closing-off membrane.

DETAILED DESCRIPTION OF THE INVENTION

(18) FIG. 1 shows a sampling device 10 having a hollow needle 20. The hollow needle 20 forms a tube of circular cross-section that constitutes the sample chamber 23. The sample chamber 23 has two openings, with the first opening of the sample inlet being 21 and possibly being pointed (not shown) to make it easier for the hollow needle 20 to be inserted into a patient. The second opening 22 is connected by a sampling line (not shown) to a second pump 90 (not shown) to allow a flushing medium to be driven through the sample chamber 23 from the sample inlet 21 to flush the sample chamber 23 or to allow a medium intended for sampling to be drawn by suction into the interior of the sample chamber 23 through the sample inlet 21.

(19) The sampling device 10 has an internal cavity 13. The internal cavity 13 is in fluid communication with an infeed-line passage 30 and outfeed-line passage 40 arranged in the interior of the sampling device 10. In the region of the internal cavity 13, the outer wall of the sampling device 10 is pierced in the form of a window and the window 14 is closed off by a separating membrane 15. From the sample chamber 23, an analyte is able to diffuse through the separating membrane 15 into the internal cavity 13 and the internal cavity 13 forms an analyte receiving chamber.

(20) In operation, the sampling device 10 is first inserted into a patient or a sampling access, such for example as a hollow needle 20, in particular a cannula or catheter or the sampling access of a bioreactor. If the hollow needle 20 is an 18 gauge hollow needle, the distance between the sample inlet 21 and the tip of the sampling device 10 is preferably approximately 3 mm. The sample chamber 23 is then flushed with a flushing medium. At the same time or following this, the analyte receiving chamber 13 is flushed with transporting medium.

(21) A sample of a medium intended for sampling, such as blood for example, is then drawn by suction into the sample chamber 23 that has been flushed, the separating member 15 thus being completely or, to a preselected degree, incompletely covered by the sample in the region of the window 14 of the analyte receiving chamber 10. If the hollow needle 20 is an 18 gauge hollow needle, 75 l is preferably enough for this.

(22) After the drawing in of the sample, a wait is made for a preselected time to give the analyte or analytes an opportunity to diffuse into the analyte receiving chamber 13. As an alternative to this, sample material may also be drawn by suction into the sample chamber 23 for a preselected time and, as a option, it may flushed out, to ensure that there is as constantly high as possible a concentration of analyte in the interior of the sample chamber 23, thus enabling as high a concentration of analyte as possible to be obtained in the analyte receiving chamber 13.

(23) Then or at the same time, transporting medium is flushed through the infeed-line passage 30 to transport the volume of transporting medium out of the analyte receiving chamber 13 and through the outfeed-line passage 40 to a sensor (not shown). The sensor is arranged for the qualitative and/or quantitative detection of the analyte. As the analyte receiving chamber 13 is flushed, the interior of the sample chamber 23 too is usefully flushed with a flushing medium to drive the sample out of the sample chamber 23 and limit any further entry of the analyte into the analyte receiving chamber 13.

(24) FIG. 2 differs from FIG. 1 only in that a spacer 11 is provided in this case to keep the sampling device 10 spaced away from the inner walls of the hollow needle 20. It is ensured in this way that the separating membrane 15 remains free in the region of the window 14 of the sampling device 10 for the analyte to pass through and is not accidentally wholly or partly closed off by the inner wall of the hollow needle 20.

(25) FIG. 3 differs from FIG. 1 only in that a filter 5, preferably a sterile filter, is mounted at the sample inlet 21. Microorganisms can be prevented from entering the interior of the hollow needle 20 in this way. Deposits or biofilms can thereby be prevented from forming in the interior of the hollow needle 20. It is also possible to in this way stop the medium intended for sampling from being contaminated by the flushing medium. This is particularly for use on bioreactors, where cells are to be prevented from making their way into or out of the medium intended for sampling.

(26) FIG. 4 shows a cylindrical sampling device 24. The sampling device 24 comprises an analyte receiving chamber 13 in which is situated a sample chamber 23 that is likewise cylindrical. The sample chamber 23 takes the form of a passage passing through the sampling device 24 and has two openings, the first opening being the sample inlet 21. The second opening 22 is connecting by a sampling line (not shown) to a second pump 90 (not shown) to allow a flushing medium to be driven through the sample chamber 23 and out of the sample inlet 21 to flush the sample chamber 23 or to allow a medium intended for sampling to be drawn by suction through the sample inlet 21 into the interior of the sample chamber 23.

(27) The analyte receiving chamber 13 is provided with an infeed-line passage 30 extending from the infeed line passage opening 71 to the analyte receiving chamber inlet opening 72 and an outfeed-line passage 40 extending from the analyte receiving chamber outlet opening 74 to the outfeed line passage opening 75. The sample chamber 23 is provided with a separating membrane 15. From the sample chamber 23, an analyte can diffuse through the separating membrane 15 and into the analyte receiving chamber 13.

(28) In operation, the procedure adopted corresponds to that which was described above for the sampling device 10 shown in FIG. 1.

(29) FIG. 5 differs from FIG. 4 only in that there is provided in this case a Luer lock connector by means of which the sampling device 24 can be connected to a sampling access by positive interengagement, a normal force and/or friction.

(30) FIG. 5a shows a sampling device according to the invention of the kind shown in FIG. 5 that has in addition a filler body 51 to reduce a dead volume in a Luer lock connector.

(31) FIG. 6a is a schematic view of the exterior of a sampling device 25 that is designed to be in the form of a probe. The probe has a tip that is designed in a similar way to the sampling device 10 shown in any of FIGS. 1 to 3. The cross-hatching 60 shows the approximate position of the separating membrane 15 of the sampling device 25. The infeed-line passage 30 (not shown) and outfeed-line passage 40 (not shown) of the sampling device 25 can be connected to fluid connectors (not shown). By means of a further fluid connector, a sample chamber 23 (not shown) that is formed when the sampling device 25 is put to use can be connected to a sampling line (not shown) through a connection 70.

(32) FIG. 6b shows various possible ways of using a sampling device in conjunction with a sampling access in the form of a multilumen catheter 80. The sampling device 25 is mounted outside the multilumen catheter 80 on or in a connection 81, both the sample chambers 23, 23 and the separating membrane 15, the position of which latter is indicated by the hatched areas 60, 60, are situated outside the actual catheter and outside the main body of the medium and, when used on a human being, outside the body of the human being too. Hatched areas 61, 62 and 63 show other possible positions for the separating membrane 15 that are reached if the sampling device 25 is inserted more deeply into the multilumen catheter 80. Associated with these positions are sample inlets 21, 21a and 21b. If the separating membrane 15 is in the position indicated by the hatched area 61, the sample inlet 21 is in direct contact with the main body of the medium.

(33) FIG. 6b also shows the use of a sampling device 25 in an outfeed line or infeed line of the multilumen catheter 80. The sampling device 25 is designed in the same way as the sampling device 25.

(34) By the single-hatched areas 64 to 68, FIG. 6b also shows possible positions for sampling devices according to the invention (not shown, see FIG. 4 or 5 for examples) that are integrally connected to the multilumen catheter 80, its infeed lines 81, or its fluid connectors 83, or to external lines 84.

(35) The arrangement thus enables a largely free choice to be made of the point at which samples are taken from the main body of the medium, from the multilumen catheter 80, from the latter's infeed lines and/or from its fluid connectors.

(36) FIGS. 7a and 7b are schematic views of the use of a sampling device according to the invention in conjunction with a cannula 82, such for example as an indwelling venous cannula or an arterial cannula.

(37) By the single-hatched areas 64, 66 and 68, FIG. 7a indicates possible positions for sampling devices according to the invention (not shown, see FIG. 4 or 5 for examples) that are integrally connected to the cannula 82, fluid connectors 83 or to external lines 84.

(38) FIG. 7b shows various possible ways of using the sampling device 25, 25 in conjunction with a sampling access in the form of a cannula 82. Sampling device 25 is inserted in the cannula 82. The hatched area 61 shows the position of the separating medium 15 of the sampling device 25. In this arrangement the sample inlet 21 is in direct contact with the main body of the medium.

(39) Sampling device 25, which corresponds to a sampling device 25, is inserted in a line 41 connected to the cannula 82, outside the main body of the medium intended for sampling. The hatched area 61 indicates the position of the separating medium 15 of the sampling device 25.

(40) FIG. 8 is a schematic view of a sampling system according to the invention. A sampling access 85 is provided with a sampling device 26.

(41) The sampling system comprises a fluidics system for samples, comprising a sampling line 111 that is connected to the sample chamber (not shown) of the sampling device 26 and that is fitted at the other end with a pump 90 that is able to pump in both directions. The other side of the pump is connected by a line 120 to a switchable connection 100 that is also connected by a line 116 to a container 130 for calibrating medium and by a line 117 to a container 131 for flushing solution. Switchable connection 100 can be switched in such a way that line 116 or line 117 or both are in fluid communication with line 120.

(42) The sampling system also comprises a fluidics system for analysis, comprising an infeed line 115 that is in fluid communication with the infeed-line passage (not shown) of the sampling device 26 and that is fitted with a pump 91 at the other end. The other side of the pump is connected by a line 118 to a container 132 for transporting medium. The sampling system's fluidics system for analysis further comprise an outfeed line 113 that is in fluid communication with the outfeed-line passage (not shown) of the sampling device 26 and that is also connected to a sensor 140. Sensor 140 is arranged for the qualitative and/or quantitative detection of the analyte. Sensor 140 is also connected via a line 114 to a container 133 for waste medium. Infeed line 115 is also provided with a switchable connection 101 and outfeed line 113 is also provided with a connector 102. Switchable connection 101 and connector 102 are connected by a bypass line 119.

(43) In operation, sample access 85, such for example as a cannula or catheter or the sampling access of a bioreactor, is first brought into contact with the main body of the medium. Switchable connection 100 is then set in such a way that lines 117 and 120 are in fluid communication and pump 90 is started and pumps the flushing solution from container 131 through lines 117 and 120 and sampling line 111 and into the sample chamber (not shown) of the sampling device 26. When this is done, the contents of the sample chamber (not shown) of the sampling device 26 and then the flushing solution are first conveyed into the main body of the medium (and possibly infused into the patient). Once the sample chamber (not shown) of the sampling device 26 is substantially full of flushing solution, pump 90 is stopped.

(44) At the same time or following this, the analyte receiving chamber (not shown) of the sampling device 26 is flushed with transporting medium by switching on pump 91 and switching switchable connection 101 in such a way that pump 91 pumps transporting medium from container 132 through line 118 and infeed line 115 and into the analyte receiving chamber (not shown) of the sampling device 26 and on from there through outfeed line 113, sensor 140 and line 114 and into container 133 for waste medium. Transporting medium should usually be pumped in this case until the entire volume of material from the analyte receiving chamber (not shown) of the sampling device 26 has passed through sensor 140 and sensor 140 indicates the measured value for pure transporting medium. Pump 91 can then be stopped and, if desired, a new cycle can be started.

(45) By reversing the direction of flow at pump 90 and starting the latter, the flushing solution is pumped towards pump 90. When this, happens, the medium intended for sampling flows into the sample chamber (not shown) of the sampling device 26, mixes there with the flushing liquid and is then pumped through the sample chamber (not shown) of the sampling device 26 and into sampling line 111, initially as a mixture with the flushing liquid and later, as the pumping continues, in a pure form. Once the sample chamber (not shown) of the sampling device 26 is substantially completely full of medium intended for sampling, pump 90 can either be stopped, as a result of which the medium intended for sampling stays in the sample chamber (not shown) of the sampling device 26 or, as an alternative to this, pump 90 may also continue to operate for a preselected time and in this way sample material can be drawn by suction into the sample chamber to ensure that there is an as constantly high a concentration of analyte as possible in the interior of the sample chamber (not shown), thus enabling as high as possible a concentration of analyte or analytes to be obtained in the analyte receiving chamber (not shown) of the sampling device 26. For the latter eventually, a volume of collecting space may also be provided in sampling line 111 for temporary storage of the medium intended for sampling. By setting switchable connection 100 in the appropriate way, the calibrating solution from container 130 may also be used for this process rather than the flushing solution. The calibrating solution may also be introduced (or infused in the case of a patient) into the main body of the medium continuously.

(46) Once the sample chamber (not shown) of the sampling device 26 is substantially full of the medium intended for sampling, a wait is made for a preselected time to give the analyte an opportunity to diffuse into the analyte receiving chamber 13 (not shown). During the optional waiting time, the transporting medium from container 132 can either be conveyed directly to sensor 140 through bypass 119 or pump 91 can be stopped. It is also possible for further medium to be drawn continuously into the sample chamber by suction and for this medium to be expelled again only after the possibly analyte-charged transporting medium has been taken away to the sensor. And it is also possible for the medium drawn in by suction to be fed back in a loop as described above.

(47) By means of a suitable sequence, it is also possible by this method for a medium intended for sampling to be brought into contact with the separating layer (not shown) of the sampling device 26 while enrichment and transport away are able to take place at the same time on the other side of the separating layer (not shown) of the sampling device 26. The fluidics systems on both sides may also be operated in continuous pulses or alternately.

(48) FIG. 9 is a schematic view of an alternative form of the sampling system shown in FIG. 8. In this case connector 102 is mounted very close to the sampling device 26 or is integrally connected thereto. In this way the sensor can be mounted at a greater distance from the sampling device 26. This layout is advisable if for example there are longer distances between the sampling device 26 and the sensor 140 or if there are a plurality of sampling devices 26 connected to one sensor 140.

(49) FIG. 10 is a schematic view of an alternative form of the sampling system shown in FIG. 8. In this case the sampling device 26 is provided in addition with an alternative outlet 121 that is in fluid communication with the sample chamber (not shown) of the sampling device 26 in the region between the sample inlet (not shown) and the separating medium (not shown) of the sampling device 26. Alternative outlet 121 is connected to pump 92 and also to container 134 for waste medium.

(50) This enables the sample chamber (not shown) of the sampling device 26 to be flushed with calibrating medium and/or flushing medium and/or transporting medium and the medium used for flushing to be pumped away through the alternative outlet rather than into the supply of medium intended for sampling. The stress in terms of volume (of liquids) on a patient can be reduced by this means.

(51) FIGS. 11a and 11b are schematic views of details of the sampling system shown in FIG. 8 showing alternative fluid storage and infeed line systems.

(52) FIG. 11a shows the construction of the fluid storage and fluid infeed-line systems when an additional container 135 is used for an additional calibrating solution. The containers 130 and 135 holding the calibrating solutions and the container 131 holding the flushing solution are connected via lines 116, 117 and 123 to the switchable connection 100, which is connected in turn to pump 90 by line 120. By means of switchable connection 100 one or others of the containers 130, 131 and 135 can be put into fluid communication with line 120. This construction is suitable for cases where a plurality of calibrating media, that contain different concentrations of the analyte for example, are used and thus for sensors that require a plurality of calibration points.

(53) FIG. 11b shows a construction for the fluid storage and fluid infeed-line systems in which the lines for the flushing and transporting media can be united. This is a system that is particularly economical of space and that allows the sampling system to be compact and to have only a few medium containers. The transporting medium also forms the flushing medium in this case and the sampling line 111 and the infeed line are thus either connected to the supply of transporting medium and flushing medium via a switchable connection 100 as shown or are connected to one common supply container (not shown).

(54) FIG. 12 is a schematic view of a further very compact alternative to the sampling system according to the invention shown in FIG. 8. The fluid storage and fluid infeed-line system is constructed as shown in FIG. 11b in this case. However, the container 133 for the waste medium is, in addition, omitted. The medium leaving sensor 140 after measurement is conveyed into the sampling line 111 by means of line 112 in this case. This produces a compact layout. However, the entire tubing system, the analyzing section and the media have to be of a sterile form in this case. What is preferably made available, in a pre-assembled form, is a fully enclosed sterile fluid system in, for example, cassette format. The entire sequence of operation must be set in such a way that the analyte-charged section is flushed out without falsifying the subsequent measurement.

(55) FIGS. 13a and 13b are schematic views of a sampling device according to the invention serving a plurality of patients and having one sensor and of a measuring arrangement serving one patient and having a plurality of sensors. The sampling devices involved here are in principle the same as the sampling device shown in FIG. 8. FIG. 13a shows that a plurality of sampling devices 26 (not shown) in a plurality of patients and/or even a plurality of sampling devices 26 (not shown) in one patient can be connected to a single sensor 140 via a switchable connection 105. This is an obvious course to take when, for example, a method of analysis is used that is particularly costly or complicated but can be automated. FIG. 13b shows that a sampling device 26 (not shown) in one patient can be connected via a switchable connection 106 to a plurality of sensors 141, 142 and 143. This is an obvious course to take when for example different analytes need to be determined.

(56) FIG. 14 is a schematic view of a 3-lumen catheter having a catheter window to allow medium intended for sampling to enter an internal passage in the catheter. The internal passage has an internal closing-off membrane that, as a result of a medium being applied (shown on the right), causes the closing-off membrane (shown hatched) to inflate after the fashion of a balloon and thus causes a reduction in the volume of the internal passage. In the embodiment shown, the closing-off membrane is of a size such that the inflated closing-off membrane closes off (shown at top right) the catheter window to prevent a medium from passing through it.

(57) Other embodiments of the invention are described below:

(58) 1. A sampling device for a sampling access, comprising an analyte receiving chamber to receive an analyte into a transporting medium, connected to an infeed-line passage and an outfeed-line passage for transporting transporting medium respectively into and out of the analyte receiving chamber, a sample chamber taking the form of an internal cavity, having a sample inlet to receive a sample possibly containing analyte, and a separating medium surrounding the internal cavity, to allow the analyte to pass through from the sample chamber into the analyte receiving chamber.

(59) 2. A sampling device as in embodiment 1, wherein the analyte receiving chamber surrounds the sample chamber.

(60) 3. A sampling device as in either of the preceding embodiments, wherein the sample chamber takes the form of a passage extending through the sampling device.

(61) 4. A sampling device as in any of the preceding embodiments, wherein the sampling device is designed for fitting to a medical sampling access and preferably to a hollow needle (cannula), catheter, port, aspirator, drain, reservoir and/or connector.

(62) 5. A sampling device as in any of the preceding embodiments, wherein the sampling device is designed for connection by positive interengagement, a normal force and/or friction to a sampling access, and preferably to a Luer lock connector and/or a screwed connector.

(63) 6. A sampling device as in any of the preceding embodiments, wherein the sampling device is designed for the arrangement of the analyte receiving chamber within a main body of the medium intended for sampling, through a sampling access, in a sampling access, at an end of a sampling access that is remote from a main body of the medium intended for sampling, and/or in a line connected to a sampling access and outside a main body of a medium intended for sampling.

(64) 7. A sampling device as in any of preceding embodiments 2 to 4, wherein the sampling device is integrally connected to the sampling access.

(65) 8. A sampling device as in any of the preceding embodiments, wherein the sampling device is designed to receive a sample of body fluid, preferably selected from blood, blood plasma, lymph, tissue fluid, cerebrospinal fluid, synovial fluid, gastric juice, gall and urine.

(66) 9. A sampling device as in any of the preceding embodiments, wherein the separating medium is a membrane.

(67) 10. A sampling device as in embodiment 9, wherein the material of the separating membrane is selected from the group comprising cellulose and derivatives thereof and in particular cellulose acetate, PTFE, polycarbonate, polypropylene, polyamides, polyesters, polyethersulfones and polysulfones.

(68) 11. A sampling device as in any of the preceding embodiments, wherein the separating medium is designed to allow the passage of an analyte selected from glucose, lactose, lactate, Na.sup.+, K.sup.+, Cl.sup., H.sub.3O.sup.+, O.sub.2, CO.sub.2, ammonium, ammonia, methanol, ethanol, formate, acetate, glutamine, glutamate, urea, uric acid, phosphate, antibodies, growth factors, hormones, medications, and in particular narcotics and anesthetics.

(69) 12. A sampling device as in any of the preceding embodiments, wherein the inside diameter of the infeed-line passage and/or the outfeed-line passage, at the analyte receiving chamber, is from 0.2 to 0.3 mm, and preferably 0.2 to 0.3 mm, and as a particular preference 0.23 to 0.26 mm

(70) 13. A sampling device as in any of the preceding embodiments, wherein the area of that portion of the separating medium that connects the sample chamber to the analyte receiving chamber (the membrane window) is 0.5 to 350 mm.sup.2, and preferably 1 to 50 mm.sup.2, and as a particular preference 2 to 35 mm.sup.2.

(71) 14. A sampling device as in embodiment 13, wherein the ratio of the area of the membrane window to the inside diameter of the outfeed-line passage is more than 400:1.

(72) 15. A sampling device as in any of the preceding embodiments, wherein the volume of the analyte receiving chamber is 2-50 mm.sup.3.

(73) 16. A sampling device as in any of the preceding embodiments, further comprising a movable closing-off membrane for reducing and/or closing off a volume of the sample chamber or the sampling access.

(74) 17. A sampling device as in embodiment 16, further comprising a passage for controlling closing-off for exerting a pressure to move the closing-off membrane.

(75) 18. A sampling device as in any of the preceding embodiments, wherein the sample chamber further comprises an alternative outlet to allow medium received in the sample chamber to leave.

(76) 19. A sampling system, comprising a sampling device, preferably as in any of the preceding embodiments, a sensor connection for connecting in a sensor for detecting an analyte in a transporting medium, an infeed line, in fluid communication with the infeed-line passage of the sampling device, an outfeed line, in fluid communication with the outfeed-line passage of the sampling device and with the sensor connection, a first pump to transport a medium through the outfeed line to the sensor connection.

(77) 20. A sampling system as in embodiment 19, further comprising a sampling line and, connected thereto, a second pump for pumping a sample into the sample chamber.

(78) 21. A sampling system as in either of embodiments 19 and 20, further comprising: a supply of transporting medium and/or a supply of calibrating medium and/or a supply of flushing medium, that are/is in fluid communication, or can be placed in fluid communication, with the infeed line.

(79) 22. A sampling system as in any of preceding embodiments 19 to 21, wherein the first pump is arranged between (a) the supply of transporting medium and/or the supply of calibrating medium and/or the supply of flushing medium and (b) the infeed-line passage of the sampling device, to allow medium to be transported from the given supply of medium through the infeed line and into the infeed-line passage.

(80) 23. A sampling system as in any of preceding embodiments 19 to 22, further comprising a bypass line for the placing in fluid communication of the supply of transporting medium and/or the supply of calibrating medium and/or the supply of flushing medium with the sensor connection, without the medium passing through the analyte receiving chamber of the sensor device.

(81) 24. A sampling system as in embodiment 23, further comprising a switchable connection for the placing in fluid communication of the bypass line with the outfeed line.

(82) 25. A sampling system as in either of preceding embodiments 23 and 24, further comprising a switchable connection for the alternative placing in fluid communication of the supply of transporting medium and/or the supply of calibrating medium and/or the supply of flushing medium with either the infeed line or the bypass line.

(83) 26. A sampling system as in any of preceding embodiments 19 to 25, further comprising an outflow line for the placing in fluid communication of the outfeed line with the sampling line via the sensor connection and possibly via a sensor.

(84) 27. A sampling system as in embodiment 26, further comprising a switchable connection for the alternative placing in fluid communication (a) of the outfeed line with the outflow line, via a sensor if required, or (b) of the outfeed line with a waste line, via a sensor if required, to convey medium leaving the outfeed line, through the sensor if required, to a means of disposing of medium.

(85) 28. A sampling system as in any of embodiments 19 to 27, further comprising a switchable connection for connecting the supply of transporting medium and/or the supply of calibrating medium and/or the supply of flushing medium to the sampling line via the second pump.

(86) 29. A sampling system as in any of preceding embodiments 19 to 28, further comprising a control system, connected to the second pump, to control the second pump in such a way that Step 1: a sample is drawn by suction into the sample chamber, Step 2: the sample that was drawn in is present in the sample chamber for a preselected time and then Step 3: the sample that was drawn in is expelled from the sample chamber.

(87) 30. A sampling system as in embodiment 29, further comprising a hollow needle, the analyte receiving chamber being arranged in the hollow needle.

(88) 31. A sampling system as in either of preceding embodiments 29 and 30, wherein the control system is also connected to the first pump to control the latter in such a way that, in step 2: Step a: transporting medium is present in the analyte receiving chamber for a preselected time and then Step b: transporting medium possibly containing analyte is transported from the analyte receiving chamber into the outfeed-line passage.

(89) 32. A sampling system as in any of preceding embodiments 29 to 31, wherein the control system is also arranged to control the first pump in such a way that Step c: after step b) transporting medium possibly containing analyte is transported from the outfeed-line passage to the sensor connection.

(90) 33. A sampling system comprising a hollow needle, a sampling device having an analyte receiving chamber in fluid communication between an infeed line and an outfeed line, the analyte receiving chamber having an opening that is closed off by a membrane permeable to analyte to allow the analyte to pass through from a region outside the analyte receiving chamber into the analyte receiving chamber, and the analyte receiving chamber being arranged in the hollow needle, a first pumping device to transport a transporting medium through the analyte receiving chamber, a second pumping device to draw in by suction and, as an option, to expel a medium intended for analysis through the hollow needle, and a control system in operative connection with the first pumping device, the control system being arranged to cause the transporting medium to be pumped through the analyte receiving chamber at a preselected time to allow a sample of the transporting medium possibly containing analyte to be obtained.

(91) 34. A sampling system as in any of preceding embodiments 19 to 33, further comprising, in fluid communication with the sensor connection, a sensor arranged to determine an analyte selected from glucose, lactose, lactate, Na.sup.+, K.sup.+, Cl.sup., H.sub.3O.sup.+, O.sub.2, CO.sub.2, ammonium, ammonia, methanol, ethanol, formate, acetate, glutamine, glutamate, urea, uric acid, phosphate, antibodies, growth factors, hormones, medications, and narcotics and anesthetics.

(92) 35. A method of sampling comprising the following steps: 1) drawing by suction of a sample into a sample chamber of a sampling device as in any of embodiments 19 to 34, the interior of the hollow, needle of a sampling system as in embodiment 33 possibly forming the sample chamber, 2) making available of a transporting medium in the analyte receiving chamber for a preselected time to allow an analyte possibly contained in the sample to enter the analyte receiving chamber, 3) expulsion of the sample that was drawn into the sample chamber, and 4) before, simultaneously with, or after step 3), transport of transporting medium out of the analyte receiving chamber.

(93) 36. A method of sampling as in embodiment 35, further comprising the step of: flushing the analyte receiving chamber and/or the sensor with analyte-free transporting medium, flushing medium or calibrating medium.

(94) 37. A method of sampling as in either of preceding embodiments 35 and 36, further comprising the step of: applying a calibrating medium to the analyte receiving chamber by feeding the calibrating medium into the analyte receiving chamber through the infeed-line passage.

(95) 38. A method of sampling as in any of preceding embodiments 35 to 37, further comprising the step of: producing a calibrated concentration of an analyte in the analyte receiving chamber by 1. feeding the calibrating medium into the sample chamber and 2. allowing analyte to pass through into a transporting medium in the analyte receiving chamber for a preselected period of time.

(96) 39. A method of sampling as in embodiment 38, further comprising the step of: allowing the calibrating medium to leave through an alternative outlet of the sampling device.

(97) 40. A method of analysis comprising the following steps: carrying out of a method of sampling as in any of preceding embodiments 35 to 39, the transporting medium possibly containing analyte being transported in step 4) to a sensor for determining the analyte.