DE19734618A1 - Analyser for in-vivo determination of analytes in body of patient - Google Patents

Abstract

The analyser includes a cannula (18) which is inserted into the skin. An optical fibre (22) couples light into the cannula, which is perforated (19) in a section that is inserted in the skin, so that interstitial liquid penetrates through the cannula wall to a measuring point on the optical fibre to produce a measurable optical change.

Description

The invention relates to an analysis device for loading mood of an analyte in the body of a (human, u. U. also animal) patients with a measuring probe, the has a cannula that can be inserted into the skin.

The concentration of components of body fluids (Analyte) is practically made for medical purposes finally determined using reagents. Doing so A sample of the body fluid (especially blood) is taken and analyzed in vitro in the laboratory. Although this procedure have been constantly improved and now for important ones Analytes, such as blood glucose in particular, small hand available analysis systems is disadvantageous lig that a blood sample for each individual examination required and no continuous measurement possible is.

Therefore, there has been a long effort, reagenzi to develop free analysis methods that predominantly  based on the principles of spectroscopy. Conventio Absorption spectroscopy on blood is in large part of the spectrum not possible because it is very contains strongly absorbent substances (in particular Hemoglobin), which are the characteristic spectral bands overlay of the analytes sought. Even if you do that Hemoglobin removed by centrifugation remain very strong disruptive optical absorption in the particularly interesting areas of the infrared spectrum.

To investigate aqueous biological fluids, especially blood, the possibilities of ATR (Attenuated Total Reflection) spectroscopy were therefore examined. Please refer in particular to the following publications:
1) Y. Mendelson: "Blood Glucose Measurement by Multiple Attenuated Total Reflection and Infrared Absorption Spectroscopy", IEEE Transactions on Biomedical Engineering, 1990, 458-465;
2) HM Heise et al .: "Multicomponent Assay for Blood Substrates in Humas Plasma by Mid-Infrared Spectros copy and its Evaluation for Clinical Analysis", Applied Spectroscopy, 1994, 85-95;
3) R. Simhi et al .: "Multicomponent Analysis of Human Blood Using Fiberoptic Evanescent Wave Spectroscopy", SPIE Proc. Vol. 2331: Medical Sensors II and Fiber Optic Sensors, 09 / 06-09 / 10/94, Lille, France, AV Scheggi et al. (Eds.), ISBN 0-8194-1664-9, published 1995, pp. 166-172.

These references show that the ATR spec troscopy is possible in principle, important analytes in the  Blood, especially glucose, without reagents, spectroscopic to be determined. ATR spectroscopy is based on that light is transported in a light guide whose outer surface is in contact with the sample. The Refractive indices in the light guide and in the sample and the Reflection angle of the light at the interface must be chosen so that total reflection of the light takes place. With total reflection an evanes penetrates center wave into the neighboring medium (the sample). An absorption that occurs leads to a Attenuation of the intensity of the trans in the light guide ported light. This weakening of light can be as long as a wave gene-dependent to be evaluated from the spectrum In information about the presence of the analyte in the sample to win. Further details can be found in the relevant Literature, especially the above citations 1) to 3) ent be taken.

Special ATR measurements are routinely used for ATR measurements cells are used in which the light guide has a prism table shape. As an alternative, many have already been fibrous light guide proposed. An example that medical analysis of blood components is the quote 3).

In the literature
4) U.S. Patent 5,436,454
describes a device with which ATR spectroscopy should be possible in vivo in the blood of a patient. For this purpose, a thin cannula similar to a syringe needle is used, which can be inserted into a blood vessel through the patient's skin for in vivo measurements. A thin optical fiber runs in the cannula to the tip, is bent back in a tight loop in the opposite direction and runs back in the cannula. Measuring light is transported to the loop by a light guide leg running in the cannula. Through the second leg, it is returned to a detector. The cannula has a diameter of approximately 3 mm and an inner bore of approximately 2 mm for receiving optical fibers with a diameter of approximately 0.7 mm to 1 mm. The publication explains that in the area of the loop there are many more reflections of the light transported in the light guide than in its straight sections. As a result, a significantly increased sensitivity is achieved in the area of the loop. At the tip of the cannula, from which the loop slightly protrudes in the measurement state, a seal prevents the sample from penetrating into the cannula. As a result, the measurement is concentrated exclusively on the area of the loop. The measurements should be carried out in the spectral range between approximately 7,000 and 700 wave numbers (corresponding to 1.5 to 15 µm). Chalcogenide glass is proposed as the material for the optical fibers.

Another example of a publication dealing with ATR spectroscopy for the in vivo analysis of parts of the body, in particular glucose, is concerned
5) WO 91/18548.

Another measuring principle, namely the measurement of the refractive index is recommended for measuring glucose in blood
6) WO 90/01697.

The invention is based on this prior art the task of an improved analysis device for the determination of an analyte in vivo in the body of a Pa to make available to clients.

The problem is solved by an analysis device, comprising a measuring probe with an insertable into the skin ren cannula and a light guide running in the cannula fiber through which a light source emanates the optical fiber coupled light into the cannula and thus is directed into the inside of the body, the in the Optical fiber transported light in the probe changes characteristic of the presence of the analyte experience and a measuring and evaluation unit to the Measure change and information from the change tion about the presence of the analyte in the body win, which is characterized in that the Ka at least on a part serving as a measuring section cut of their length that can be inserted into the skin per is perforated, so that interstitial fluid through the Cannula wall to a measuring section running in the cannula cut the optical fiber and that for the counter characteristic change of the analyte Light from an interaction with the interstitial Liquid results in the measuring section.

In the context of the invention it was found that it is in Ge Contrary to the recommendation given in publication 4) is advantageous if the measurement is not on a loop is concentrated at the tip of the cannula, but a longer measuring section of preferably between 3 mm and 10 mm in length within the length of this meas cut perforated cannula is available. The The measuring medium is not the blood in one vein, but rather  the interstitial fluid in the skin tissue, preferably wise in subcutaneous skin tissue. In doing so, a verbes achieved accuracy and sensitivity, among others whose because it was found in the context of the invention, that with a closely localized measurement a high risk of measurement errors due to local disturbances both with regard to the measuring probe, as well as with regard to the surrounding skin fabric exists.

The objectives of the invention, especially a good measurement tity and tolerance for the patient with a con continuous measurement over a longer period of time (at least one day each, preferably at least three days) can be achieved even better if the subsequent, preferred measures individually or in com combination can be used together.

The measuring method is preferably based on the ATR spec microscopy. The characteristics of the presence of the analyte static change in the transport in the optical fiber light is its wave-dependent Weakening in the measuring section. Regarding the usual measurement and evaluation methods can be used in full on the relevant literature, in particular on the above publications cited.

The wavelength of the measuring light is preferably in the range mid-infrared (MIR), especially between about 7 µm and 13 µm. This wavelength range is in particular suitable for the analysis of glucose as analyte.

The material of the optical fiber is said to be in the spectral spectrum range of the measuring light should be as transparent as possible. For the The purpose of the invention is in particular a silver halogen nid compound, especially AgCl, AgBr or mixtures  of which, suitable. Mixtures with are particularly preferred a predominant share in AgBr. These materials ha ben in the spectral range mentioned a very rings absorption and can be in the form of very thin ela tical fibers are produced. A potential pro problem when used in contact with body fluids ten is that this is always a significant concentration ions contain ions and therefore on silver halogens nid connections have a corrosive effect. Within the scope of the invention however, it was found that silver halide fibers even without additional protective measures in immediate Contact with the interstitial fluid for one Period of several days without a function hazardous degree of corrosion can be used.

The use of silver halide fibers for non-medical analyzes is known, for example, from the following literature locations:
7) R. Göbel et al .: "Enhancing the Sensitivity of Chemical Sensors for Chlorinated Hydrocarbons in Water by the Use of Tapered Silver Halide Fibers and Tunable Diode Lasers", Applied Spectroscopy, 1995, 1174 to 1177;
8) JF Kastner et al .: "Optimizing the optics for Evanescent Wave Analysis With Laser Diodes (EWALD) for monitoring chlorinated hydrocarbons in water", SPIE Vol. 2783 (1996), 294 to 306;
9) DE 40 38 354 C2.

Another, albeit less preferred, material for the optical fiber comes into chalcogenide glass.  

According to the latest knowledge, diamond can also be found in Form a suitable fiber. For the purposes a relatively short, very thin piece of optical fiber material. In the event of von Diamant prefers the fiber from Herstel a square or rectangular cross cut. More details are on at the same time handed German patent application "devices to Un testing a sample substance using attenuated To Talreflexion "by the Fraunhofer Society for Promotion of applied research e.V., Munich, attorney's mark: IPM-P119.

In the context of the invention, the optical fiber in general do not have a round cross-section. The term "fiber" is in the sense of understanding that it is a piece of light conductive material with a length that is to the Pricking the length of the cannula required in the skin (at least about 3 mm) and its cross section is very small in relation to the length. Prefers the cannula should have a maximum outside diameter 0.8 mm, particularly preferably at most 0.3 mm. At A wall thickness of 0.05 mm results in an In cross section with a diameter of 0.7 mm approximately 0.2 mm. The fiber cross section must be such that it fits into this small lumen of the cannula, although in the case the cannula is preferably a non-round fiber a corresponding non-round cross-sectional design Has.

Further preferred embodiments, which are explained in more detail using the exemplary embodiments shown in the figures, provide the following features:

• - The cross section of the optical fiber in the measuring section is not the same throughout, but varies. It so one or more times finds a transition from one larger fiber cross section to a small one ren optical cross-section instead. Through this in other connection in the above Pu The measure already described will be applied Number of reflections in the optical fiber and infol the sensitivity of the measurement increased.
• - The optical fiber is of a semi-permeable membrane bran so enveloped that the interstitial rivers liquid in the measuring section only through the membrane the surface of the optical fiber can get. The semipermeable membrane has an exclusion limit for large molecules with a molecular size of more than 5,000 Da, preferred for molecules with one mole cooling size of more than 1,000 Da. By this measure with the given metrological effort, the accuracy ity increased or it is possible to choose a desired one To achieve measuring accuracy with reduced effort, because the larger molecules (especially Proteins) can be avoided. For example it is possible, the number of necessary for the evaluation to reduce wavelengths. In addition redu the semipermeable membrane adorns the rejection craze tion of the body against the pierced skin Probe. This results in an extension of the attainable length of stay in the body. As a material the membrane comes in particular polysulfone polyamide, Polyethylene, polycarbonate and cellulose.
• - The optical fiber is in the measuring range with a Provide coating that perform multiple tasks can. For one, it can protect against corrosion  serve the fiber. Second, she can make an Ab Stand up to direct contact between the optical fiber and one enveloping it to prevent semi-permeable membrane. Third, can a material for the coating can be selected, which leads to an enrichment of the analyte on the Surface of the optical fiber leads.

The invention is described below with reference to the figures schematically illustrated embodiments explained; show it:

Fig. 1 is an analysis apparatus according to the invention in perspective view;

Fig. 2 is a perspective view of the electric nikeinheit of the apparatus of Fig. 1,

Fig. 3 is a cross-sectional view of the probe head of the apparatus of Fig. 1,

Fig. 4 is a schematic representation of the irradiation and detection means at a first execution of the invention,

Fig. 5 shows an alternative embodiment of the infeed cash measuring probe,

Fig. 6 shows a further alternative embodiment of the pierceable probe,

Fig. 7 is a schematic diagram of appropriate for the probe of FIG. 6 light irradiation and detection means.

The analyzing apparatus 1 shown in Fig. 1 consists essentially of a probe head 2 having a puncturable in the skin measuring probe (insertion probe) 3, and a measuring and evaluation unit 4. The measuring and evaluation unit 4 has two spatially separate parts in the preferred case shown, namely a joint with the probe head 2 on the patient's body portable electronic unit 5 , which preferably contains only those electronic elements that are necessary to the measuring light in the probe 3 and to measure a change characteristic of the concentration of the analyte on the measuring light returning from the probe 3 . The resulting measurement signals are stored in the electronics unit 5 and transmitted for evaluation - preferably wireless - to a central evaluation electronics 6 , which is the second component of the measurement and evaluation unit 4 and electronic means for receiving the measurement signals and for further processing in the each required manner.

Details of the function of the measuring and evaluation unit and the distribution of this function to the two components 5 and 6 shown Darge depend on the individual case. For example, it may be expedient that the electronics unit 5 contains a sufficient degree of intelligence to determine the concentration values of the analyte to be determined and to display them on a display. The evaluation electronics 6 performs long-term tasks, in particular the long-term storage of the measurement data, the display of curves, etc. If the analysis device is designed to determine the blood glucose in diabetics, it may be expedient, for example, to display the blood glucose values continuously on the electronics unit and at the bottom - or to trigger an alarm signal if certain limit values are exceeded. The evaluation electronics then serve to store data for use by the doctor and to possibly calculate insulin doses for the therapy of the patient.

Further details of the electronics unit 5 and the measuring probe 2 can be seen in FIGS. 2 and 3. In the electronics unit 5 , which is shown in FIG. 2 with the cover removed, there is at least one light source 8 for generating the measuring light. In the illustrative case, five semiconductor light sources 9 (light-emitting diodes or laser diodes) are provided, the light of which is combined by a beam combining unit (beam combiner). The resulting light beam is fed into a fiber optic cable 11 through which the electronics unit 5 is connected to the probe 2 .

In the probe head 2, the penetration probe 3 by means of two supporting discs 14 and 15 mounted (Fig. 3). The upper holding disc 15 also serves as strain relief and guide for the fiber optic cable 11th For attachment to the skin, a skin contact disk 16 is provided, which for example can have an adhesive underlayer 17 , in order to attach the probe 3 to the skin surface.

The penetration probe 3 consists essentially of a cannula 18 perforated with holes 19 , made of a physiologically harmless metal (for example stainless steel) in which two fiber paths 20 and 21 of an optical fiber 22 run parallel and one in the region of the distal end 23 of the cannula 18 arranged prismatic reflector gate 24 . The reflector 24 is coupled to the distal ends of the fiber paths 20 and 21 in such a way that light coupled into one of the fibers (leading fiber path 20 ) is reflected back into the other fiber (leading fiber path 21 ).

In the embodiment shown, two optical fiber paths run parallel within a flexible sheath 12 in the fiber optic cable 11 . The measuring light is coupled from the beam combining unit 10 into the first (introductory) optical fiber section 25 of the cable 11 and passed into the introductory fiber section 20 of the measuring probe 3 . After reflection at the reflector gate 24 , it is passed back through the returning fiber path 21 of the measuring probe 3 and a corresponding returning fiber path 26 of the fiber optic cable 11 into the electronic unit 5 , where the measuring light is detected by a detector 27 .

In the preferred embodiment shown, the introductory fiber sections 25 and 20 and the conductive fiber sections 26 and 21 of the probe 3 and the fiber optic cable 11 are each formed in one piece, ie they each consist of a continuous fiber of a uniform fiber material. This is preferred in view of easy manufacture and low intensity losses.

However, there is also the possibility of producing the fiber sections extending in the measuring probe 3 from a different material than the material extending outside the measuring probe (in the fiber optic cable 11's ) and extending the light in the area of the proximal end 28 of the cannula 18 in to couple the respective subsequent fiber section. This is particularly useful if there are technological difficulties in producing a sufficiently long piece from the fiber material that is used for the lines 20 , 21 of the light guide 22 running in the probe.

The perforation holes 19 extend over a partial section of the cannula 18 . The corresponding partial length of the optical fiber 22 running in the cannula 18 (in the illustrated case both fiber sections 21 and 22 ) is referred to as the measuring section 30 . In the measuring section 30 , the outside of the optical fiber 22 is in the skin weave via the perforation holes 19 with the cannula 18 surrounding interstitial fluid in contact. In order to enable an intensive exchange, the cannula 18 is perforated as much as possible. For a very thin cannula with a diameter of 0.3 mm, a hole diameter of approximately 0.1 mm is used. The holes can be created in particular by laser drilling processes. The area of the perforation holes on the surface of the cannula in the measuring section 30 should be sufficiently large. A pore fraction of at least 20%, preferably at least 50%, is currently sought.

In addition to diagnosing the analyte, the cannula 18 can also be used to apply a drug (in particular in sulin) subcutaneously. In this case, the housing of the electronics unit 5 contains an insulin pump, not shown, and the fiber optic cable 11 contains a hose, not shown, for transporting the medicament into the cannula 18 . The medicament flows in the cannula 18 past the optical fiber 22 and passes through the perforation holes 19 into the tissue. This breaks the contact between the interstitial fluid and the surface of the optical fiber. This can advantageously be used for zero calibration of the optical measurement.

A laser light source is preferred as the light source for the measuring light, in particular because it enables a high spectral luminance and can be focused on the end faces of very thin optical fibers. Laser light sources are monochromatic and generally have a fixed, unchangeable wavelength. FIG. 4 shows how a spectroscopic measurement with several laser light sources of different wavelengths is possible in the invention.

In the illustrated embodiment, three lasers 31 to 33 are provided for three different wavelengths. The output of the first laser 31 is directed directly into the optical axis of the arrangement. The light from the other two lasers 32 and 33 is deflected by means of semitransparent mirrors 34 and 35 into the same optical axis. A coupling optic 36 is provided for coupling into the introductory fiber section 25 , 20 . A second coupling optic 37 is used to couple the measuring light supplied via the diverting fiber paths 21 , 26 to the detector 27 . The spectral sensitivity of the detector 27 is sufficiently broadband that it can detect all the wavelengths of the lasers 31 to 33 .

Of course, you can measure with more than three Wavelengths corresponding to more lasers can be used. Quan is preferred for measurements in the middle infrared cascade laser for use.

Another special feature of the embodiment shown in Fig. 4 compared to Fig. 3 is that before the entry of the optical fiber 22 in the cannula 18, a transition from a thicker in the cable 11 extending fiber path 25 to a thinner fiber section 20 in the Cannula 18 takes place. Correspondingly, a transition from a thinner fiber section 21 in the cannula 18 to a thicker fiber section 26 in the cable 11 takes place on the exit side. In Fig. 4 le diglich is shown for reasons of clarity that the fiber sections 25 and 26 extend in the opposite direction. As a rule, it will be more convenient to run them through a single cable 11 .

The taper 38 shown in Fig. 38 of the optical fiber 22 before entering the cannula 18 has the part before that a relatively thick optical fiber can be used in the fiber optic cable, which is characterized by better mechanical stability and lower optical losses . In addition, it has proven to be advantageous not only because of the lower pain in a thin cannula 18 , but also for reasons of measurement sensitivity, if the optical fiber in the cannula 18 has a very small cross-section (corresponding to a diameter of less than 0.2 mm) Has.

In the embodiment shown in FIG. 4 with the taper 38 , it is advantageous if - as already explained above - the fiber lines 20 , 21 are made separately from the fiber lines 26 , 26 and possibly consist of a different material. The coupling points in the area of the proximal end 28 are designated 55 in FIG. 4. The fiber sections 20 , 21 in the cannula 18 are separated by a metal strip 56 mirrored on both sides. This prevents optical crosstalk. In addition, the fiber sections 20 , 21 , which are preferably semicircular in cross-section for this purpose, are first attached to the separating strip 56 when the sensor is mounted and then inserted together into the cannula.

In Fig. 5, a penetration probe 3 is shown in which, as in Fig. 3 in the cannula 18, two Lichtleitfa serstrecken 20, run 21 in parallel, with the light through an initial length of fiber 20 toward the distal end 23 of cannula 18 is transported becomes. As with Fig. 3 of 23 of the cannula 18 is in the region of the distal En a deflection in the opposite direction, instead of the light and is discharged through the track made of conductive fiber 21 from the cannula 18. The embodiment shown in FIG. 5 differs from the embodiment according to FIG. 3 with regard to the following features.

The deflection of the light in the area of the distal end 23 of the cannula 18 is achieved here by a narrow deflection loop 39 of a continuous optical fiber 22 . In contrast to quote 4), the area of the deflection loop 39 is not used for the measurement. On the contrary, a mirrored cap 40 ensures that the light is deflected with the lowest possible reflection losses and without decoupling.

The optical fiber paths 20 and 21 each have a taper point 13 at which the cross section of the optical fiber changes from a larger value to a smaller value in order to thereby, as described, increase the number of reflections and the sensitivity of the measurement. Instead of the relatively fast transitions shown, a slow taper over the entire measuring section 30 can also be advantageous. It is also possible to provide a plurality of areas in each optical fiber section running in the measuring section 30 , in which the cross section of the optical fiber varies.

The optical fiber 22 in Fig. 5 is provided with a coating device 41 which on the one hand must not interfere with the measurement, on the other hand fulfills one or more of the above-mentioned tasks. Two types of coating materials are particularly suitable.

The coating can consist of a very thin (for example evaporated) metal layer. The metal (preferably noble metal, especially silver) protects the optical fiber 22 against corrosion. It is also suitable as a spacer for a membrane 42 surrounding the optical fiber 22 . Since the exit of evanescent waves is already considerably affected by a very thin metallic coating, it should be interrupted in the case of ATR measurements, so that direct contact between the interstitial liquid and the surface of the optical fiber is possible on a considerable part of the surface is. In conjunction with a thin metallic coating, however, another interaction mechanism between the light transported in the optical fiber 22 and the interstitial liquid, namely via plasmonic surfaces, is also possible.

Alternatively, it may be advantageous to provide the optical fiber 22 (at least in the measuring section 30 ) with a coating made of a polymeric material. The polymer used may only have a low absorption in the spectral range of the measuring light. The polymeric coating also serves to protect the fiber from corrosion and, as a spacer, prevents direct contact between the membrane cover 42 and the optical fiber 22 . According to the current state of knowledge, the following materials are particularly suitable as suitable poly mers: poly tetafluoroethylene, polyisobutylene polycarbonate.

A polymer coating is particularly preferred has analyte-enriching properties. For non-medical professionals ATR measurement procedure in citations 8) and 9) described. A coating that has these properties has to experiment for the desired analyte tell can be found.  

A further peculiarity of the embodiment shown in FIG. 5 is that one of the Lichtleitfa water 22 in the measuring section 30 enveloping membrane 42 is seen before. As already mentioned, the membrane prevents the access of high molecular substances to the surface of the optical fiber 22 , whereby an improved measurement accuracy can be achieved with a relatively low metrological effort. Of course, suitable sealing measures must be taken to ensure that the interstitial fluid cannot reach the optical fiber 22 to a practically disruptive extent through remaining gaps. In the illustrated case, for example, the cannula 18 is closed by a drop of 44 epoxy resin, which at the same time ensures the lower sealing device of the membrane 42 .

Suitable membrane materials that have the mechanical, chemical mixing and dialysis properties for the present application are known from so-called microdialysis processes. In particular, reference can be made to:
10) U.S. Patent 4,694,832 and the references cited therein.

Particularly suitable membrane materials have been described above already mentioned.

In the context of the invention, it was found that the advantageous effect of a membrane 42 enveloping the optical fiber 22 can be significantly influenced by the membrane touching the optical fiber 22 directly. The light transport of the measuring light in the optical fiber 22 can thereby be affected in a very unfavorable manner for the measuring accuracy. Therefore, it is particularly preferred in the context of the present invention that the membrane is substantially spaced from the outer surface of the optical fiber 22 . "Substantially Chen spaced" is to be understood to mean that any remaining contact surfaces between the membrane and the outer surface of the optical fiber 22 are so small that the measurement accuracy is not impaired to a disruptive extent. The contact area should in any case be less than 50%, preferably less than 20% and particularly preferably less than 10% of the surface of the optical fiber 22 in the measuring section 30 . As shown in FIG. 5, a coating 41 of the optical fiber 22 can serve as a spacer. The distance between the membrane 42 and the optical fiber 22 is not necessary if the membrane has no disturbing absorption in the spectral range of the measuring light.

In FIG. 6, an alternative way of producing a distance between the optical fiber 22 and the membrane 42 is shown. The membrane 42 is coated on the inner surface of the cannula 18 here . The light guide fiber 22 is fixed with spacer rings 43 in the cannula 18 . Alternatively - although less preferred according to the current state of knowledge, there is also the possibility of applying the membrane to the outer surface of the cannula 18 , the distance from the surface of the optical fiber 22 then of course being ensured by the wall of the cannula 18 .

A further peculiarity of the embodiment shown in Fig. 6 is that within the cannula 18 , which is closed at the bottom in this case, in section 30 only one optical fiber path 45 extends, at the distal end 46 of which a mirror coating 47 is provided, through which the light in the same optical fiber path 45 is reflected back.

In the embodiment shown in FIG. 6, it is necessary to couple the measuring light in a suitable manner into the single optical fiber path 45 and to couple it out again. One possibility for this is shown schematically in FIG. 7. From the light of a broadband emitting light source 50 , the desired wavelength range is selected by means of a bandpass spectral filter 51 . The resulting light falls through a beam splitter 52 via a coupling optics 53 into the optical fiber 22 . After reflection on the reflector 47 , the light falls back through the coupling optics 53 onto the beam splitter 52 and is reflected by the latter into the detector 27 . Instead of the broadband light source 50 , an arrangement of several lasers (as in FIG. 4) can also be used in this case.

Claims (16)

1. An analysis device for determining an analyte in vivo in the body of a patient, comprising
a measuring probe having a pierceable into the skin Ka Nuele (18) and extending within the cannula (18) optical fiber (22) through which light emanating from a light source (8) into the optical fiber (22) eingekop peltes light into the cannula ( 18 ) and thus directed into the interior of the body, the light carried in the optical fiber ( 22 ) in the measuring probe ( 3 ) undergoing a characteristic change for the presence of the analyte and
a measuring and evaluation unit ( 4 ) to measure the change and to obtain information about the presence of the analyte in the body from the change, characterized in that
the cannula ( 18 ) is perforated at least on a section serving as a measuring section ( 30 ) of a length that can be pricked into the skin, so that interstitial fluid passes through the cannula wall to a measuring section of the optical fiber running in the cannula ( 18 ) and for the presence of the analyte characteristic change of light results from an interaction with the interstitial fluid in the measuring section. 2. Analysis device according to claim 1, characterized in that the cross section of the optical fiber ( 24 ) in the measuring section ( 30 ) varies. 3. Analysis device according to claim 1 or 2, characterized in that in the cannula ( 18 ) in the Meßab section ( 30 ) only one optical fiber path ( 45 ) runs ver, at the distal end of which a mirror coating ( 47 ) is provided, through which the Light is reflected back into the same optical fiber path ( 45 ). 4. Analysis device according to claim 1 or 2, characterized in that in the cannula ( 18 ) in the Meßab section ( 30 ) two optical fiber paths ( 20 , 21 ) run par allel, the light through the one optical fiber path ( 20 ) in the direction of dis the tale end (23) of the cannula (18) is transported, the cannula (18) deflects the other way in the area of the distal end (23) and is discharged through the other fiber span (21). 5. Analysis device according to claim 4, characterized in that a prismatic reflector ( 24 ) is arranged for deflecting the light in the region of the distal end ( 23 ) of the cannula ( 18 ). 6. Analysis device according to one of the preceding claims, characterized in that the Lichtleitfa water ( 22 ) is coated in the measuring section. 7. Analysis device according to claim 6, characterized in that the coating ( 41 ) is metallic. 8. Analysis device according to claim 6, characterized in that the coating ( 41 ) is polymer. 9. Analysis device according to one of claims 6 to 8, characterized in that the coating ( 41 ) has analyte-enriching properties. 10. Analysis device according to one of the preceding claims, characterized in that the measuring section ( 30 ) of the optical fiber ( 22 ) is encased by a semipermeable membrane ( 42 ) such that the interstitial liquid in the measuring section is only through the membrane ( 42 ) reaches the surface of the optical fiber ( 22 ). 11. Analysis device according to claim 10, characterized in that the membrane ( 42 ) is arranged within the cannula ( 18 ). 12. Analysis device according to claim 10, characterized in that the membrane ( 42 ) from the outer upper surface of the optical fiber is substantially spaced. 13. Analysis device according to one of claims 10 to 12, characterized in that the membrane on poly carbonate based. 14. Analysis device according to one of the preceding claims, characterized in that the material of the optical fiber 22 is selected from the group consisting of silver halide, chalcogenide glass and diamond. 15. Analysis device according to one of the preceding claims, characterized in that the wavelength of the light emanating from the light source ( 8 ) is between 7 µm and 13 µm. 16. Analysis device according to one of the preceding claims, characterized in that the light source ( 8 ) has at least one quantum cascade laser ( 31-33 ).