System for monitoring analyte concentration in body fluidThe application is a divisional application of the invention with the international application date of 2002, 2.2.2 and the international application number of PCT/EP02/01091 (Chinese national application number of 02804615.3).
Technical Field
The present invention relates to diagnostic methods for extracting a body fluid and analyzing for the presence or concentration of an analyte and systems for monitoring the concentration of an analyte in a body fluid.
Background
Various methods for monitoring the concentration of analytes in body fluids are known in the art. On the one hand, systems exist in which blood is withdrawn by means of a catheter and conveyed to a measuring element. An instrument that can be worn on the arm and that draws a blood sample using a catheter inserted into a blood vessel is described in document WO91/16416, to which document WO91/16416 is mentioned as a typical example of such a method. The bodily fluid sample is transported through a substantially closed channel system to an enzyme electrode capable of performing a variety of measurements. The system described in this document and other systems based on electrochemical sensors that make continuous measurements have the disadvantage that the sensors have a significant signal drift. This drawback is particularly evident in document WO91/16416 when taking account of the difficult calibration. Another disadvantage of such sensor-based systems is that a relatively large volume of body fluid is required. In the prior art, sensors are considered to be systems that require only small amounts of body fluid, and this view is therefore initially surprising. However, when emphasizing the positive features of the sensor system, one generally does not take into account that flow channels are necessary and that a sufficiently large size of the sensor surface has to be wetted.
Ultrafiltration devices are also known in the art, for example as disclosed in US4,832,034 and US4,777,953. These systems also use electrochemical sensors and therefore also have the above-mentioned drawbacks. In addition, these systems suffer from the disadvantages associated with ultrafiltration membranes. It is critical to select a suitable membrane material that has a combination of high enough filtration efficiency and permeability and that does not clog for a short period of time.
Another method for monitoring the concentration of an analyte, known as microdialysis, is also known. Representative literature in this field is: US5,174,291, EP 0401179 and US4,265,249. Flow measuring cells with electrochemical sensors are used in the devices described in these documents. Although the ultrafiltration problems caused by membranes are rare for microdialysis, microdialysis systems have the disadvantage that the perfusion liquid has to be pumped through the hollow catheter. The provision of solutions, the pumping process and the construction of the conduits are all technically complex factors that add complexity.
The above-described method for monitoring the concentration of an analyte in a body fluid is based on the premise that the monitoring requires continuous or at least approximately continuous measurements at short time intervals. This illustrates the exclusive use of continuously operating sensors in flow measurement units.
The discontinuous concept is also known in the field of analyte concentration monitoring. For example, diabetic patients are measured intermittently several times during the day to monitor their blood glucose levels. For this purpose, an incision is usually first made with a lancet and the exiting blood is supplied to the disposable test element. It is analyzed with a suitable device to determine the blood glucose concentration. Optical systems and systems using electrochemical test elements are known in the prior art. Devices have been known for some time in which incision formation, sample collection and sample application are carried out using a disposable test element. Such systems for determining blood glucose in interstitial fluid are disclosed, for example, in documents US5,746,217, US5,823,973 and US5,820,570. The device has a thin cannula that is inserted into the dermis and collects interstitial fluid at that site. The cannula delivers the fluid to the test element. One disadvantage of this system is that the cannula must be reinserted for each individual measurement. In addition to the discomfort due to repeated punctures, the user must perform a number of steps, such as inserting a disposable element into the device; starting a joint cutting program; waiting until the analysis result comes out; and replacing the test element. In addition, the device must be carried around by the user, so if the user does not want to be sick, a discreet place must be found.
US5,368,029 describes a system which also has the above-mentioned disadvantages, but uses a system comprising a catheter and an initially separate test element. According to this document, a catheter is first introduced into the blood vessel, waiting (drawing blood) before the transparent chamber is filled with blood. Next, a disposable test element is inserted into the chamber through the valve seam to bring the test element into contact with the blood. The daily use of such a system by diabetics is difficult to imagine, since a catheter must be inserted into the blood vessel, which carries a great risk of infection and injury. In addition, a larger amount of sample is required. The specification in this document discloses that the system is suitable for emergency treatment. Another major drawback of this concept is that the system is not capable of analyte concentration monitoring, but only simple measurements reflecting instantaneous concentration levels. This document does not give any information or suggestions etc. about how to perform repeated measurements by connecting new test elements. This is logical, since the blood collected in the chamber (33) is not exchanged, so that subsequent measurements with additional test elements can only yield the same measurement values, rather than measurement values from which later concentration values can be derived.
Disclosure of Invention
The invention is based on a system with continuously operating sensors and a system using a separate piercing method. The invention relates to a system for monitoring an analyte concentration in a body fluid, in particular in interstitial fluid, comprising a catheter with an implantable region and an outlet opening for withdrawing fluid, in particular body fluid. The first and second analysis regions are in succession contacted by fluid from the conduit and undergo a detectable change in the presence of analyte. The contacting of the analysis zone with the fluid can be effected manually but preferably automatically by means of a device. The system according to the invention also has an analysis device for analyzing the analysis zone in order to determine the concentration of the analyte on the basis of the change caused by the analyte. The invention also relates to a catheter and a cartridge with a test area for use in a system according to the invention.
The present invention provides a system for monitoring an analyte concentration in a bodily fluid, comprising: a carrying unit carried on the body having a catheter including an implantable region and an output aperture for withdrawing fluid; said carrying unit further comprising a strip comprising two or more analysis zones in contact with the fluid, said analysis zones exhibiting a detectable change when the analyte is present in the body fluid; and an analysis device located in the carrying unit or separate, the analysis device analyzing changes in two or more analysis regions caused by the analyte-containing fluid to determine the concentration of the analyte to be monitored.
The present invention also provides a cartridge for an analysis zone, comprising: an input port for a fluid; at least one first and second analysis region; and means for bringing the first and second analysis regions into proximity with the inlet so that fluid entering the cartridge contacts each analysis region.
The present invention combines the advantages of a continuous operation system and a system for performing individual measurements using disposable test elements. The present invention uses a catheter that remains implanted between measurements (at least two), thus eliminating the need for repeated dissection as was the case with previous systems with disposable test elements. The problems of previous continuous operation systems, which are mainly used in combination with continuous operation sensors, can be avoided by using a separate test element. However, this combination of known elements is not disclosed in the prior art nor is it obvious to one of ordinary skill in the art. Previously, the expert has assumed that for continuous monitoring of analyte concentrations, which has to be carried out using a flow measuring cell comprising a continuously operating sensor system, measurements have to be carried out at short time intervals. First, providing such a large amount of analyte at short time intervals is clearly not suitable for disposable test elements. The concept to which the present invention relates revolutionizes analyte concentration monitoring, since monitoring can be performed with a relatively simple system, in particular without drift of the electrochemical sensor. Dry chemical test elements can be used for the test element or the test area, which has proven to be particularly suitable in terms of accuracy and precision and also has advantages in terms of manufacturing.
The present invention relates to systems and methods for monitoring analyte concentrations in bodily fluids. Analytes that can be monitored using the present invention are, for example, glucose, lactate, electrolytes, pharmaceutically active substances, and the like. The body fluids to which the present invention relates are in particular interstitial fluid and blood. If interstitial fluid is used, body fluids obtained from a depth of more than 1mm below the skin surface are preferred, since there is a good and sufficiently fast exchange with the blood transport system at this site.
A catheter with an implantable region is used to withdraw fluids. The catheter to which the invention relates is a tube into which body fluid can enter and from which it can be discharged from an outlet opening and a device with a semipermeable membrane, so that the fluid entering the catheter is not body fluid in the strict sense but a fluid which has been pretreated (ultrafiltered). In principle, it is also possible to use a microdialysis catheter as a catheter which works with perfusion fluid and takes up the analyte from the interior of the body by diffusion and produces the dialysate. Catheters with semi-permeable membranes or microporous walls have the advantage that cells or even larger molecules that affect the detection can be excluded. Therefore, it is preferable to use a film or a microporous wall having a pore size of 500 nm or less.
However, one problem with microdialysis catheters circulating a dialysis fluid is that, when the residence time is short, the fluid discharged from the catheter may not reflect the true analyte concentration in the body under certain circumstances but only a fraction thereof. Thus, for the present invention, the catheter is preferably designed in such a way that (for example in the case of ultrafiltration) a body fluid can flow directly out of it, which body fluid can also be devoid of cells.
The term "catheter" as used in the present invention shall not only refer to components that are implanted in the body, but shall also include fluid connection components and other connection components belonging to such components. In the simplest case, the catheter may consist of a thin hollow needle or tube, which is inserted into the body at one end and from which the body fluid flows out through an outlet opening at the other end. A tube or the like may be connected to such a conduit to transfer the output port to the respective end of the tube. The structure and function of suitable or preferred catheters will be described in detail below with reference to the drawings. Preferably, a so-called applicator device is used to insert the implantable region of the catheter into the body. In this way, implantable regions of very small diameter, for example, below 100 microns, can also be formed. In this thickness range, even materials such as steel are flexible. If an applicator device is not used, the flexible structure cannot be used for practical reasons of not being able to insert the flexible structure into the body. Applicator devices suitable for flexible and rigid structures are known in the art. Reference is made herein to US3,651,807; EP A0366336; WO 95/20991 and WO 97/14468 are examples of suitable applicators described.
Another feature of the invention is the use of two or more analysis zones capable of undergoing a detectable change upon contact with fluid taken from the outlet. Various forms of suitable analysis areas are known from the field of disposable test elements. Analysis regions which undergo an optically detectable change are particularly suitable for use in the present invention, for reasons which will be explained in detail below. One example of an analytical detection zone particularly suitable for use in the present invention is described in US6,029,919. For the layers of the test element, it is of course also possible to use less complex test elements. Electrochemical test elements are also useful in the present invention. Electrochemical test elements such as described in US5,288,636 are preferred compared to continuously operable measurement cells and the like used in the fields of ultrafiltration and microdialysis, since no drift problems exist.
The use of the term "analysis zone" in contrast to "test element" clearly indicates that the analysis zones do not have to be elements separate from one another, but that the test zones can actually be arranged on the same body (test element). In a particularly preferred embodiment of the system to which the invention relates, a strip is used in which the test chemical is arranged in the form of a strip and adjacent regions of the strip are contactable with fluid discharged from the catheter. It is also explicitly indicated that the term "analysis zone" is not limited to embodiments in which the analysis zone is predetermined, but that embodiments are particularly preferred in which the respective analysis zone is undefined before being brought into contact with the fluid. Thus, positioning problems can be avoided to a large extent. Alternatively, however, it is also possible to use test elements which are separate from one another and which each provide one or more analysis regions. As mentioned above, it is preferred that the disposable embodiment be used with analysis areas, wherein one analysis area is not reused after use. As described above, the analysis region of the present invention does not exhibit problems such as drift occurring in the flow measurement unit. This is due to the fact that unused analysis areas are used and that the properties of the analysis areas can be adequately controlled with the manufacturing process, as is well known in the art. Thus, it is possible to determine the manufacturing tolerances of the analysis areas at the factory and store them, for example in the form of bar codes, in order to take these differences into account during the analysis in order to increase the accuracy of the analysis.
An important aspect of the present invention is the sequential supply of liquids to the test zones for contact with the liquid from the conduit. This can be achieved in particular by bringing together the individual analysis regions with the outlet opening of the catheter in order to bring the analysis regions into contact with the fluid. The term "focusing" as used herein refers to moving the analysis zones to the output port so that they can pick up fluid therein. However, if the outlet is located on a flexible tube, the outlet may be directed to an analysis zone for said fluid contact. The term "pooling" also includes the process of transporting the analysis zone, for example in the form of a belt, past the output opening (while in contact with or in direct proximity to the output opening) to supply liquid to the analysis zone.
Embodiments may also be used in which liquid has been removed from the conduit by means of separate contact. This can be achieved in particular by means of an absorbent or capillary analysis zone. However, it is preferred to design the system such that liquid is not expelled from the outlet port until a negative pressure is applied. This enables the supply of liquid over the analysis area to be controlled by adjusting the pressure environment in the system.
Another way of contacting the analysis zone with liquid from the conduit is to drain (drip) part of the liquid from the conduit in such a way that the fluid part hits the test zone. This may in particular be used with ink jet or bubble jet systems in which the fluid portion is ejected from an outlet opening of the conduit or a subsequent ejection unit. A possible design for such an ejection unit is disclosed in document US4,336,544, see the known printing technique.
As already described with reference to US5,368,029, it is important to monitor the change in analyte concentration over time to ensure that a defined time frame of liquid reaches an analysis zone and that the liquid is mixed with the smallest possible amount of liquid according to the previous time interval. The invention can be realized in a comparatively simple manner by means of a catheter having an inner cross-section of less than 0.5 mm. For such small cross-sections, little convection occurs to pass the liquid through the conduit in the form of a bolus. In this connection, it is also important to avoid dead volumes in the conduit as much as possible, for example by means of an inverted cone at the fluid connection, etc. Another important measure in this connection relates to the ratio between the volume of liquid discharged from the conduit and the effective internal volume of the conduit. The amount of liquid displaced is preferably substantially equal to or greater than the effective internal volume of the conduit so that the effective volume is substantially completely evacuated when displaced liquid is applied to an analysis zone. On the one hand, this ensures that the extracted liquid is derived with the time interval between the current extraction and the previous extraction. The effective internal volume of the conduit refers to the internal space of the conduit that is filled with liquid between two liquid withdrawals and emptied during one withdrawal. In addition to the geometric design of the interior space of the catheter, the effective interior volume of the catheter is also determined by means of a liquid barrier element, such as a hydrophobic barrier. The preferred design of the catheter and the extraction process will be described later with reference to the drawings.
Another feature of the present invention is an analysis device for analyzing an analysis area after contact with a liquid. Such analytical devices are known from the prior art, for example for use in blood glucose measuring devices. Reference is made here to US4,852,025 as an example thereof, in which the conversion of reflectance photometry into concentration values is described. Such an analysis device comprises: a light source for illuminating the analysis region; a detector for detecting radiation reflected from the analysis region; and circuitry for converting the detector signal to an analyte concentration. Such an analysis device or an additional application detection device may advantageously be used to determine whether the analysis area has been sufficiently contacted with the liquid. However, it is not only possible to detect the application of liquid onto the analysis area as described in EP 0256806, but it is also possible to determine the amount of liquid wetting the analysis area relatively accurately. In the present invention, the wettability of the analysis region is preferably detected for several reasons. On the one hand, it enables checking of the operating sequence and even control of the operating sequence. For systems operating at negative pressure to cause liquid to flow out of the outlet opening, the detection of the wettability of the analysis zone or the measurement of the amount of liquid on the analysis zone can be used as a signal to switch off the negative pressure and thus the liquid transport. In addition, the signal can also be used to interrupt the contact between the analysis area and the liquid or the outlet opening.
There are many ways to detect the application of liquid to the analysis area or the amount of liquid that has been applied to the analysis area. For example, US5,114,350 describes monitoring the surface reflection of a test area. A similar process is also described in US4,199,261. Furthermore, it is known from document WO83/00931 that the amount of radiation absorbed by a test specimen in the infrared range can be used as a measure of the amount of liquid. The above-described method can be used in the present invention.
Drawings
Figure 1 shows the configuration and mode of operation of the catheter.
FIG. 2 is a perspective view of an analytical system having a strip-shaped test element.
Fig. 3 shows a cassette with strip-shaped test elements and conduits.
Fig. 4 shows an analysis system with a connection to a tube system for blood withdrawal.
Fig. 5 shows an analysis system with a separate unit for manual operation.
Detailed Description
Figure 1A shows the configuration of a preferred catheter in accordance with the present invention. The catheter includes: a hollow needle, the end portion 10 of which is implanted in the tissue 2 of the patient. The hollow needle of FIG. 1 is made of stainless steel and has an outer diameter of 500 μm, an inner diameter of 100 μm and a length of 7 mm. For example, plastic may be used instead of stainless steel. The proximal region 11 with the enlarged inner cross section adjoins the end portion of the hollow needle. As shown in FIG. 1A, the delivery vessel 14 is attached to the delivery outlet 13 of the hollow needle, said delivery outlet 13 being located slightly above the junction area between the implantation area and the proximal area 11. The catheter device is attached to the body surface using a disc-shaped holder 15. For this purpose an adhesive may be provided on the underside of the holder 15. For further retention, above the holder 15 there is a connecting element 16, which connecting element 16 ensures a fluid-tight connection between the outlet tube 14 and the outlet opening 13 of the hollow needle 10, 11.
The function of the catheter device can be understood from the steps shown in figures a-D. Fig. 1A shows that body fluid, in particular interstitial fluid, enters the implantation zone 10 of the hollow needle and is transported into the proximal zone 11 of the hollow needle by capillary force or by vacuum. To allow bodily fluids to enter, the implanted portion 10 has one or more input ports 17. These input ports may be located on the needle tip as well as in the wall region of the hollow needle above the needle tip. The length of the implanted portion and the location of the input port may be used to determine the depth of delivery of the bodily fluid. It has been shown that it is preferable to deliver body fluids from a depth greater than 1 mm. It was also found that the epithelial layers (epidermis and dermis) having a total thickness of about 1mm only weakly exchange substances with the interior of the body, and that the exchange of blood flow is particularly weak. Determining the metabolic state of a diabetic patient from blood glucose values has become a routine practice in diabetes monitoring. This is mainly due to the fact that the blood flow supplies the brain and thus hypoglycemia can pose an acute threat to life. It is therefore preferred for the present invention to take sample fluid from a depth greater than 1mm, and most preferably from a depth in the range 3 to 10 mm.
As shown in fig. 1A, the body fluid rises in the hollow needle and fills the proximal region 11 of the hollow needle. This is usually only performed by capillary forces in the hollow needle. For this reason, it is advantageous that the inner region of the hollow needle which needs to be wetted by the sampling fluid is preferably hydrophilic. In the case of a metallic hollow needle, this can be achieved, for example, by applying a hydrophilic coating. If the capillary force is insufficient, a negative pressure may be applied to facilitate the transport of body fluid from within the body.
In fig. 1A, a vent hole 12 is provided at the upper end of the hollow needle, which vent hole 12 allows air displaced by body fluid to escape. The vent is preferably hydrophobic to prevent body fluids from escaping the hollow needle. The air holes may be, for example, plastic tubes made of a hydrophobic polymer such as polyethylene. Another important function of the vent is to limit evaporation from the hollow needle to avoid clogging the system due to drying of the fluid.
FIG. 1B shows the device of FIG. 1A in a full condition ready for detection. It can be seen in particular that, firstly, only the interior space of the hollow needle is filled, while the connecting tube 14 is not filled. This is achieved by using a connecting tube with a hydrophobic (or hydrophobically coated) inner wall. As shown in fig. C and D, fluid is withdrawn from the full condition of fig. 1B. Applying a negative pressure at the output port 14' of the connecting tube 14 empties the upper widened portion (proximal portion 11) of the hollow needle. The fluid force in the system is preferably adjustable so that only the hollow space in the needle above the output port 13 can be emptied. After emptying the space, air is sucked in to cause the body fluid to flow in the form of a bolus through the connecting tube onto the test area connected to the outlet 14'. The liquid forms a spot 21 on the test area 20, which spot 21 has different optical properties than the surroundings and can thus be detected. After the upper interior space of the needle has been emptied, it can be slowly refilled with fluid which then flows in from the implanted part. It has been found that measurements at intervals of about 5 minutes are well suited for monitoring the blood glucose concentration of a person, so that the time required to fill the upper part of the needle is less critical.
The system shown in fig. 1 operates in batch mode and the volume provided by one discharge can be adjusted using the volume of the upper needle region 11. Alternatively, the liquid from the implanted needle may be drawn directly onto the test area, for example by contacting the test area with the output opening.
Fig. 2 shows a system for monitoring concentration, which has a measuring unit 101 and a disposable unit in which a test area in the form of a test element tape is arranged. A connecting tube 114 engageable with the hollow needle as an alternative element to the connecting tube 14 shown in fig. 1 is shown on the front side of the disposable unit 121. The unit 121 is closed so that negative pressure with respect to the external space is supplied to the internal space thereof through the negative pressure connection 118. Two rollers are located in the inner space of the unit 121, the first roller, dispensing roller 119, carrying a roll of strip-like analyte. The tape from the first roller 119 passes behind the tube's exit port 114 and is wound onto a second roller, the waste roll 120. Absorbent analytical tapes are particularly suitable for use in the present invention because liquid is captured and absorbed, avoiding contamination of the interior space and ensuring sanitization of the fluid. To operate the roller mechanism, the unit 121 has a rubber collar 122 in which a drive rod rotates, which is driven by the measuring unit 101 and winds the analytical tape onto the roller 120 in a stepwise manner. The measuring unit 101 is equipped with an optical head 102, the optical head 102 being inserted into a recess in the disposable unit 121. The optical head 102 has a light source for illuminating the analysis zone and a detector for recording the reflected radiation. For this purpose, an optical window 103 is provided on the front side of the optical head 102. Since the analysis tape passes through a region close to the outer space and negative pressure can be applied, a transparent window is provided in the unit 121 between the analysis tape and the optical head. The measuring unit also has an electronic analysis unit for determining the analyte concentration from the reflected radiation. The results of the determination can be displayed directly on a display or they can be sent to a data processing unit 130 for displaying or converting the results, for example. The measuring unit also has a connector 105 for the tube 118 and a pump connected to the connector, which can be used to pump air out of the disposable unit 121. The measuring unit 101 also has a connector 104 for a rubber flange 122 and a drive mechanism for a drive rod rotating in the flange. After the measurement unit and the disposable unit have been connected together with the catheter, the analyte concentration is monitored in the following manner:
the disposable unit 121 is supplied with negative pressure by the pump of the measuring unit so that the body fluid collected in the catheter is sucked into the unit 121 via the tube 114 and onto the strip-shaped test element (analysis strip). After the fluid bolus has been supplied to the test region, the evaluation optical system 102 is used to check whether the sample has been correctly applied to the test region on the basis of the wetting point. A reflectance photometric analysis of the test area is now performed with the analysis optics 102 and the measurement results are converted into concentration values for the analyte concentration. Without the embodiment operating in batch mode as described with reference to fig. 1, the fluid application on the test area may also be monitored and when a sufficient amount of fluid is detected, the contact between the test area and the fluid may be interrupted, for example by relieving the negative pressure. It typically takes several minutes after the measurement is completed and before a short length of the tape-like test element is wound onto the waste tape roll 120 by actuating the drive mechanism so that a new test area is moved adjacent the output opening of the tube 114. The liquid can then be transported by again providing a negative pressure and can be taken up with a new analysis zone at the output of the tube 114.
Fig. 3 shows a disposable unit 121' similar to the disposable unit shown in fig. 2. A hollow needle 110' implantable in the body has been incorporated in the disposable unit. The implantable region 110 'is arranged perpendicular to the base surface 124' of the disposable unit. Thus, the hollow needle 110' can be directly implanted into the body by pressing the base surface of the disposable unit against the body surface to simplify the operation. The hollow needle 110 'is engaged with the connection tube 114', and the connection tube 114 'is held by the holder 125'. The strip-shaped test element 108 'is guided through the output point of the connecting tube 114' to test the sample application point 140 at this location. The analytical tape is guided through rollers 126'. If measurements are made every 5 minutes, then a 100 cm long analytical tape 108' can monitor analyte concentration over a 24 hour period. To prevent degradation of the analytical tape 108 ' during this time, a desiccant 127 ' may be provided in the disposable unit 121 '. Also due to the aging of the assay material, it is desirable to seal and store the disposable unit 121/121' in a water-tight and vapor-tight manner prior to use. This can be achieved simply by sealing the disposable unit in a plastic laminate after manufacture.
Fig. 4 shows a system for monitoring analyte concentrations, such as may be used in the field of emergency therapy. In the field, catheters are commonly placed in blood vessels to draw blood to monitor analyte concentrations or to administer drugs. When blood is drawn through the flow tube 200, a system may be connected to it so that the analyte concentration can be directly monitored in the blood. A T-piece is provided through which blood is drawn using the draw tube 114 ". The monitoring method is similar to that described in the previous figures. However, with the system shown, blood is drawn directly from the blood stream, rather than filling and emptying a predetermined volume of space in batches as shown in FIG. 1.
FIG. 5 illustrates one embodiment of a smaller overall monitoring system. The body-carried unit 301 comprises a catheter 310 implantable in the body tissue 2, the catheter 310 being held in a plate 315 attached to the body. A holder 302 for a test element with a receiving opening 303 is located above the conduit opening. When the first test element 320 is inserted, the analysis zone 321 is placed over the catheter opening and the body fluid discharged from the catheter wets the analysis zone. When the total amount of body fluid has been applied to the test area, the test element is inserted into the conventional analytical instrument 400 and analyzed manually, for example by visual observation by the user. When additional measurements are required, the user may insert a second test element 320 'into opening 303 to wet test area 321'. Although the user himself has to perform more steps than with the system shown in the preceding figures, the embodiment of fig. 5 has an extremely simple structure and is able to use commercially available units for test elements and analytical instruments. One major advantage of the system shown in fig. 5 over previous systems on the market is that the operator does not have to repeatedly puncture the body for separate body fluid withdrawal, but rather the unit 301 provides the body fluid required for analysis as required.