HK1181986B - Diagnostic device - Google Patents

Description

Diagnostic device

The invention relates to a method and a device for exposing an active surface of a diagnostic element to a body fluid for measuring the concentration of an analyte, comprising a hollow guide needle penetrating through the skin of a patient and accommodating the active surface and a connection line to a measuring means of the diagnostic element.

Monitoring the levels of endogenous analytes such as glucose, lactate, creatinine or oxygen in certain individuals is critical to their health. Certain substances such as glucose may also be administered for diagnostic stress testing. In addition, monitoring the levels of xenobiotics such as insulin and certain drugs and their metabolites is important for diagnosis of e.g. renal and hepatic function and is crucial for the choice and correct dosage in drug therapy. For a selected drug, monitoring its pharmacokinetics under the treatment conditions in a given patient may allow individualized optimization of the treatment plan and help avoid potentially serious drug-drug interactions. For such applications, a reliable device that allows monitoring of analyte concentrations in body fluids such as subcutaneous interstitial fluid for several hours to several days is necessary. Convenience and minimal invasiveness are very important features in order to achieve patient acceptance and use in an outpatient setting.

A convenient alternative to frequent blood sampling is to measure the concentration of analytes in dermal interstitial fluid, since the concentration of certain analytes such as glucose is highly correlated between these two fluid spaces (Bantle et al, JLabClinMed 1997; 130: 436-. Sensors such as for glucose monitoring in interstitial fluid are known in the art, such as U.S. patent 6579690 to bonnecize et al, published 6-17 2003, and U.S. patent application 20070249922 to Peyser et al, published 10-25 2007. (see also the review by Heller and Feldman, chemical reviews2008, 108: 2482-. Various embodiments of such a sensor device are disclosed in the patent application. An important feature of these devices, as well as of the devices of the prior art, is that the sensor is first implanted in the body and, in a second step, on the patient, has to be connected to a control unit. Such procedures, especially with miniaturized components, require a high level of skill and the use of installation tools is foreseeable, but the operation is complicated in several steps. These defects severely limit acceptance and can easily lead to incorrect functioning. A fully implantable sensor including a wireless transmitter avoids the problem of mounting several components together after the sensor is implanted. On the other hand, their size necessarily entails that the surgical procedure for implantation has an associated inconvenience for the patient and requires a qualified health care professional to perform the implantation. The damage to the subcutaneous tissue when the sensor is implanted depends on the size and shape of the sensor or the implanted lead and results in an inflammatory tissue reaction that may alter the performance of the sensor or even result in a change in the availability of the analyte surrounding the sensor. Therefore, for reliable measurements, minimal invasiveness is important. This can only be achieved by miniaturization of the implanted part of the sensor and optimization of the sensor shape and the insertion device to avoid tissue damage upon insertion as much as possible.

Most sensors and interposers of the prior art are far from optimal in this respect.

To overcome the inherent operational problems of implantable sensors, several approaches are taken to extract subcutaneous fluid or fluid with an electric current, for example by making a hole in the skin with a cut or with a laser beam. Since the volumes that can be extracted by these means are small, typically less than 1 μ l, the determination of analyte concentration is technically difficult and unreliable, and many factors such as perspiration can lead to variations in composition and a severely erroneous determination.

A solution to overcome some of the above problems by incorporating custom functional elements such as sensors, implant devices and measurement devices into a single device unit attached to the skin of a patient is described in the Hadvary and Tschirky patent application (EP 1706019 (a 1), published as 10/17/2006). The described solution is however only applicable to rigid sensors that can be used directly for piercing the skin for implantation. Most established technologies leading to rigid miniaturized sensors are based on core materials that are fragile in these dimensions, such as silicon, and are therefore not suitable for subcutaneous sensors. Other established techniques for sensors are based, for example, on a flexible plastic substrate that can only be inserted into the skin by means of a rigid lead, which is then removed after implantation of the flexible sensor. To allow the removal of rigid guides, U-shaped telescopic guides are commonly used, as described for example in the patent applications by Huss, Stafford et al (CA 2636034 (a 1), published 10/25/2007), which limit the extent of possible miniaturization, since, in addition to manufacturing difficulties, the very thin walls of the sides of the U inevitably lead to cutting edges and therefore to significant tissue damage.

It is an object of the present invention to overcome the current problems by miniaturizing the insertion of subcutaneous sensors and other diagnostic elements that require a guide for implantation.

This is achieved according to the invention in that the hollow guide needle is only partially retracted after its insertion, thereby exposing the active surface at the tip of the diagnostic element to body fluid without disturbing the connecting wire of the diagnostic element. The device for performing the method has a hollow guide needle loosely accommodating in its cavity the active surface and the connecting wire of the diagnostic element and means for partially retracting the guide needle after implantation.

During partial retraction, the guide needle slides over the connecting wire of the diagnostic element, but the connecting element to the measuring device at the other end of the connecting wire remains outside the needle and therefore does not require a U-shaped guide with a slit opening that allows complete retraction and removal of the guide.

A hollow needle having a smooth, cylindrical surface minimizes tissue damage and feel when inserted into the skin. In contrast, due to the thin wall, the miniaturized U-shaped cannulated guide inevitably results in a scalpel-like cutting edge, which results in significant tissue damage and bleeding. The problem of removing the hollow introducer needle after implantation is overcome by partially retracting the introducer needle to allow the active surface of the diagnostic element to be exposed to interstitial fluid. Solutions are also disclosed for fixedly positioning the prefabricated connections of the conductive element with other functional elements within the device, resulting in user-friendly and safe operation, even for miniaturized structures. Furthermore, customized functional elements are disclosed, such as means for first controlling the insertion of the introducer needle and the diagnostic element and subsequently partially retracting the introducer needle as a second step, and means for functional packaging to facilitate safe operation. In a preferred embodiment, the diagnostic element has an active surface consisting of a flexible plastic surface with a width of less than 0.3mm and a conducting part, there is a prefabricated connection between the conducting part and other functional elements within the device, and the introducer needle, the insertion mechanism, the control and measurement means are all contained in a single device unit attached to the skin of the patient. Furthermore, preferably, the insertion mechanism described by Hadvary and Tschirky (EP 1706019 (a 1), published 2006, 10, 17) is used to insert the guiding needle into the skin without the need to move the diagnostic element relative to all other elements comprised in the device. This allows a simpler construction and a higher reliability with security properties than a moving element or connection that has to be established by the user. After placing the device on the skin using the disclosed functional packaging ensuring safe adhesion to the skin, the implantation of the sensor and the activation of the measurement can be achieved with a single and easy operating step, e.g. pressing a release button. Such a configuration also allows unprecedented miniaturization and optimization of the design of the implanted part of the diagnostic element and of the guide needle, thus becoming minimally invasive and thus painless and highly reliable. In addition, the partially retractable guide needle of the present invention can accommodate many different types of miniaturized diagnostic elements in an optimal manner.

The terms used in this specification should be understood in accordance with the following definitions:

an "adhesive layer" for temporary wear on the skin is made of a material that has strong tack, stretchability, and minimal sensitization. The adhesive layer is fixed on the flexible base of the device in such a way that it does not interfere with its flexibility. Preferably, the surface of the adhesive layer fixed to the skin is significantly larger than its surface fixed to the flexible base of the device. This may be achieved, for example, by an adhesive layer extending beyond the surface of the base of the device or, preferably, by using an adhesive surface to the skin that is shaped like or just slightly larger than the surface of the flexible surface of the device but fixing it to the latter in such a way that the outer annular region is not fixed to the base of the device. Such a design for a medical device with a rigid base is described in EP 0825882.

By "analyte" is meant any endogenous or exogenous substance, the concentration of which can be used to diagnose the health, organ function, metabolic state, or drug metabolizing ability of an individual. Examples of endogenous substances are glucose, lactic acid, oxygen, creatinine, etc. Examples of exogenous substances are drugs, metabolites of such drugs, diagnostic substances (e.g. insulin) and the like.

"body fluid" is interstitial fluid or blood.

The "component with a flexible surface" consists of a housing, preferably with a circular or oval footprint and with a flexible base. The base plate is constructed in such a way that it can be deformed into a convex shape with protruding parts, for example like a cone or gable (position 1). An additional feature of the base is that it can be changed from a convex shape to a flat shape (position 2) with sufficient speed and force that the movement can provide the driving energy for the implanted sensor. Such a flexible surface may be achieved by appropriate segmentation of the surface that acts as a spring with the hinge region and/or by using an elastic material with the necessary reversible tensile properties, which moves for example from a pre-stressed shape to assume a flat, relaxed shape.

The means for positioning the flexible surface relative to the introducer needle in two defined positions consists of an element that can cause the flexible surface to deform to a convex, pre-stressed shape and allow the entire surface to be quickly released from that position in a coordinated manner to assume a flat, relaxed shape. This may preferably be achieved by several pin-like elements protruding from the flexible surface and pushing onto the sliding bolt mechanism, but other configurations using screws, ramps, levers, etc. are also possible.

Such a component with a flexible surface may be manufactured by injection moulding of a suitable plastic, but may also be manufactured by using other materials such as steel, composite materials or ceramic materials. The base of the element has an opening, preferably in the form of a hole or slit in the center, as an opening for guiding the needle. The guide needles are axially positioned to the base in such a way that in position 1 they are completely concealed, while in position 2 they protrude from the base.

The "control and measurement means" contain all necessary electronics and software elements for all necessary functions of the device, such as, but not limited to, initializing, controlling and monitoring the correct function of the device, feeding and controlling diagnostic elements and converting sensor signals into analyte measurements, storing, displaying and transmitting analyte measurements online or in batches, preferably wirelessly interacting with an external control device, and issuing a warning signal if the device is not working properly or if the analyte measurements are not within a predefined range.

A "diagnostic element" is a functional element for determining the concentration of an analyte and represents, but is not limited to, any sensor, body fluid removal or microdialysis system.

The tip of the diagnostic element comprising the active surface is in direct contact with the body fluid and exposes, for example, a sensor, an opening or a semipermeable/dialysis membrane allowing passage of the analyte from the body fluid to the fluid passing through the diagnostic element by a technique known as microdialysis. The active surface is part of an assay or sample collection system and is connected to other system components within the non-implanted portion of the diagnostic element by a conductive portion of the diagnostic element.

The sensor may comprise one or more electrochemical, ion selective, sonar or surface plasmon resonance probes with electrically or optically conductive elements, and may be composed of functionally similar or different elements selective for one or several analytes.

The active surface of the sensor for example comprises at its surface a probe that provides a certain signal (e.g. electrochemical, optical, thermometric, piezoelectric or magnetic) depending on the concentration of the analyte. The surface of the sensor may be smooth or moulded in such a way that the sensor is mechanically protected. In addition, the surface may be augmented by appropriate geometry to increase the signal generated by the sensor. Various methods for the composition and construction of suitable sensors have been described in the literature. These also include methods of preventing leakage of components of the sensor when implanted in the skin and at the same time allowing diffusion of the analyte of interest, for example by using a suitable biocompatible polymer or by coating with a semi-permeable membrane.

In the case of an electrochemical sensor, the sensor is configured as an electrode that is selective for a selected analyte, such as glucose. In the case of an optical sensor, the active surface may be configured as an optical fiber and may also contain elements for selective optical detection of analytes in the form of suitable coatings and sensors and/or measurement chambers. In the case of thermometric, piezoelectric or magnetic sensors, the active surface is constructed in such a way that it can convert the corresponding signal in an optimal way.

An additional advantage of the invention is that several sensors can be accurately positioned with respect to each other and the array can be constructed in such a way that they form parts of one measurement system, e.g. the working electrode and the "counter electrode", or the light source and the light collector.

In the case of microdialysis systems, the active surface is a dialysis membrane which forms the interface between the body fluid and the dialysate, the dialysate passing on the other side of the membrane. In a preferred embodiment, the microdialysis probe consists of an outer tube and an inner tube, covered by a dialysis membrane at the implantable tip. The inner tube is connected to a pump delivering the dialysis fluid and the outer tube is connected to an analysis or collection element.

The "functional packaging" is designed to retain the rigid portion of the device by a releasable coupling mechanism, and has a removable cap to protect the active surface of the sensor or diagnostic element during storage in a defined environment such as humidity, and to allow sterility to be maintained. The functional package also has a rim element allowing the rim of the adhesive layer to be attached correctly by pressing against the skin after removal of the cap. Furthermore, the functional packaging protects the release/activation mechanism of the device from premature, accidental operation and can only be activated after the device is attached to the skin and the functional packaging is removed.

An "introducer needle" is a hollow needle with thin walls and an outer diameter of less than 1mm that loosely houses the active surface and part of the conductive portion of the diagnostic element in its cavity, and has a tip and is configured to be sufficiently rigid to allow easy penetration of the skin. If the diameter of the introducer needle is small, preferably less than 0.3mm, insertion into the skin can be accomplished in a minimally invasive and painless manner. The guide needle is preferably equal to or shorter than the conductive part of the diagnostic element. When the guide needle containing the active surface and part of the conductive part of the diagnostic element is inserted into the skin, the guide needle is only partially retracted, whereby the tip with the active surface of the diagnostic element is exposed to body fluid while the conductive part of the diagnostic element remains within the guide needle.

The "sliding bolt mechanism" continuously adapts to several fixed positions based on circular or linear motion and consists of elements that show a closed or open state, such as a solid surface or a hole. The movement of the sliding mechanism is driven, for example, by a spring and is actuated by a release element, for example, by pressing or releasing a button or handle or by a slight rotational movement. The movement of the sliding bolt mechanism from the storage position (position 1) to the next position (position 2) based on an easy operation, e.g. by pressing a button actuating the flexible surface to quickly release from the pre-stressed shape to assume a flat, relaxed shape, allows the movement of the sliding bolt mechanism to the next position (position 3) to be actuated, e.g. based on releasing a partially retracted button actuating the guide needle.

Preferred embodiments of the present invention are described below with reference to the accompanying drawings, in which:

figure 1 shows a cross-sectional view of the device in a ready-to-use mode;

figure 2 shows a cross-sectional view of the device in its operating mode;

FIGS. 2a, 2b show the enlargement indicated in FIG. 2;

FIG. 3 is an illustration of a sliding bolt mechanism actuating insertion of an introducer needle into the skin and partial retraction of the introducer needle in a sequential manner;

fig. 3a-c show an enlargement of the area indicated in fig. 3, above a sectional view and below a top view.

This embodiment is a diagnostic device that can be worn and operated by a patient. The main object of the present invention is to use a solution with miniaturized diagnostic elements having supports (e.g. flexible printed plates or dialysis membranes) that are not suitable for direct insertion into the skin and avoid slit guiding needles that cannot be miniaturized below a certain limit. It is an object of the present invention to insert a diagnostic element into the skin of a patient substantially painlessly, thus avoiding the natural rejection of invasive procedures by the patient and minimizing the body's response to injury. Another object is to maintain an accurate positioning of the active surfaces of the diagnostic elements with respect to the device, the skin and each other, resulting in measurements with improved reliability. Furthermore, the fixed connection between the active surface of the diagnostic element and the measuring device, which is made possible according to the invention, greatly improves the reliability of the diagnostic element and makes the construction much simpler. In addition, the necessary manipulations of the patient, such as pressing buttons, are reduced to a minimum of easy manipulations, which do not require flexible fingers for implanting diagnostic elements and/or interfacing with control and measurement instruments.

In contrast to known sensor devices, in the device of the invention the miniaturized active surface and the conductive part of the diagnostic element are implanted in the skin in a needle having smooth walls without sharp-edged slits, at the necessary level of miniaturization. The reason for using slit guide needles is that they can be removed, leaving an active surface implanted. According to the invention, a needle without a slit may be used if the needle is only partially retracted leaving the active surface exposed to body fluid. The guide needle, which accommodates the active surface and part of the guiding portion of the diagnostic element, is inserted into the skin by relaxing the pre-stressed flexible surface attached to the skin by means of the adhesive layer. The introducer needle is partially retracted after insertion into the skin, exposing the active surface to the subcutaneous fluid.

In the ready-to-use state shown in fig. 1, the flexible surface protrudes beyond the tip of the introducer needle. In this position, the device holds the skin away from the tip when it is placed on the appropriate body area (preferably the abdomen, thigh, upper arm or forearm) and is attached by means of the adhesive layer by gentle pressure. For inserting the introducer needle into the skin, the base plate is released from its pre-stressed position, preferably by pressing an activation button. This activates the mechanism that releases the flexible surface into a relaxed flat shape. The skin attached to the flexible surface moves relative to the introducer needle and is penetrated by the tip. It has been found that in case the flexible surface is pre-stressed by a stretchable adhesive layer to form a conical or gable shape by radial segmentation, the construction according to the invention makes it possible to move the skin with sufficient pushing force such that even a miniaturized guiding needle of a diameter smaller than 0.25mm can be inserted into the skin accurately with substantially no feel and with little damage to the skin tissue. The construction allowing to operate the implantation process by pressing a release mechanism, such as a button, perpendicular to the skin surface results in better performance due to adhesion to the skin, e.g. compared to a rotational movement, and the exact geometrical positioning of the implanted part of the sensor is greatly improved. After insertion of the introducer needle into the skin, partial retraction is preferably actuated automatically and strictly continuously, for example by a sliding bolt mechanism as shown in fig. 3. The active surface of the diagnostic element becomes exposed to the subcutaneous fluid after partial retraction of the introducer needle as shown in fig. 2 showing the device in the operational mode. The great advantage of the construction according to the invention over similar known devices is that it is not necessary to use a slit guide needle and that all connections to the implanted part of the diagnostic element are rigid and that no new connections have to be established after insertion-with known devices such connections have to be established after implantation of the sensor and the slit guide needle cannot be sufficiently miniaturized without leading to cutting edges.

As shown in fig. 1, the diagnostic device has a housing with a cylindrical side wall 1, a disc-shaped flexible substrate 2 in a pre-stressed position imposed by pins 3 of the flexible substrate, which is attached to the skin 5 by means of an adhesive layer 4. The guide needle 6 houses the active surface 7 and the adjacent part of the connecting line or conductive part 8 of the diagnostic element forming a rigid connection to the control and measuring device 9. The guide needle 6 is fixed in a holder 10 at its end opposite the tip and is held in the lowered position by a slide bolt plate 11 which also holds the pin 3 of the flexible substrate. The actuation button 12 actuates the implantation and the successive partial retraction of the introducer needle described in more detail with reference to fig. 3, after which the measurement procedure is initiated. In the ready-to-use state, the actuation button and the holder of the introducer needle are pressed upwards against the stop by springs 13 and 14, respectively.

The base plate is preferably annular or oval and has radial segments, preferably divided into 5 to 8 segments, spaced between them and having a central concentric opening, forming a conical shape when the centre is bent, or alternatively it consists of two segments with diagonal slits, forming a gable shape when bent. The segments are attached to the circumference of the housing by elastic hinge regions and are additionally preferably made of a flexible material. On its underside, the flexible substrate has an annular or oval adhesive layer for fixing the device to the skin of a patient with a concentric central opening or diagonal slits, respectively, similar to the substrate. The adhesive layer is composed of three parts: adhesives for attachment to flexible substrates, fabrics to provide the necessary flexibility, and adhesives for attachment to the skin. Suitable materials with low sensitization potential are commercially available. The adhesive layer is protected during storage with a suitable sheet. In this example, the adhesive layer has a larger circumference than the device, but it may also have the same circumference if attached to the substrate leaving it unconnected to the outer region of the housing.

Fig. 2 shows the diagnostic device in an operational mode. The flexible substrate 2 is shown in a relaxed, i.e. flat, position. In the ready to use mode, the pin 3, which imposes the pre-stressed position of the flexible substrate, is now free in the slot of the slide bolt plate 11, and the holder of the guide needle 10 has been passed through the hole of the slide bolt plate by the keyway configuration and held in place by a stop (not shown). The active surfaces of the introducer needle and the diagnostic element protrude through the openings or slits of the substrate and adhesive layer and are inserted into the skin. An important feature of the invention is that the connection between the active surface of the diagnostic element implanted in the skin and the rest of the device is fixed and therefore does not have to be made manually after the implantation procedure. In addition, the present invention does not require removal of the introducer needle. This is a great advantage for reliability, ease of operation and user acceptance compared to similar devices of the prior art.

The enlarged sectional view of fig. 2a shows the holder of the guide needle 10, which fixes and retracts the guide needle 6 sliding on the conductive part of the diagnostic element 8 in a geometrically well defined movement. This configuration also allows for accurate positioning of, for example, the sensor array at geometrically well defined locations.

The enlarged view of fig. 2b shows the partially retracted guiding needle 6 and the active surface of the diagnostic element 7 directly exposed to the subcutaneous tissue. In this example, the conductive part of the diagnostic element 8 is held in a partially retracted guide needle and a flexible printed board is used as the active surface and as a base for the conductive part of the diagnostic element. The active surface of the diagnostic element holds the electrochemical sensor 15 and the conductive portion of the diagnostic element holds the insulated electrical conductor wire 16. It is also possible to place more than one sensor and conductor line on the same and/or opposite side of the flexible printed board substrate.

Fig. 3 shows an embodiment of the device for bringing the flexible substrate from the ready-to-use position to the position of the operation mode and for continuously partially retracting the introducer needle. This is in the described embodiment a circular sliding bolt mechanism consisting of three parts: a plate 11 with several slits, an actuation button 12 and a drive mechanism 21, for example a spring to turn the plate. In this figure a mechanism for a flexible substrate having four radial segments is shown, but the principle of the mechanism can be easily adapted to more radial segments, to two segments having diagonal slits and to a linear sliding bolt mechanism.

In the ready position, the flexible substrate (not shown) is pre-stressed by a pin on the section bounded by the cross beam 17 of the slide bolt plate. After a first rotation, for example 30 °, the pins fall into the slits 18 and the substrate thereby quickly relaxes to a flat position. The holder of the guide needle (not shown) is pressed by a spring against the slide bolt plate, has a cylindrical shape fitting into the central hole of the plate, and has four tabs which are limited by the cross beam 19 of the plate in the starting position and also after the first rotation of the slide bolt plate. When rotated a second time, for example again 30 °, the tabs fall into the slots 20 and the retainer of the guide needle is pressed against a stop (not shown) by a spring through the central hole of the slide bolt plate.

The drive mechanism 21 is released by pressing and then releasing the actuation button 12 again, thereby enabling continuous actuation of the first and second rotations of the slide bolt plate. The actuation button is in the slot 22; the narrowed portion 23 holds the slide bolt plate in the starting position (fig. 3 a), the protruding pawl 24 stops the first rotation of the slide bolt plate (fig. 3 b), and the second rotation of the slide bolt plate is stopped by the end of the slit 22 (fig. 3 c). Details of how pressing and releasing the actuation button successively actuates these rotations are shown in fig. 3A to 3C showing cross sections of the device housing 1, the actuation button 12 and the sliding bolt plate 11 with the slit 22. Furthermore, a schematic horizontal section at the level (dashed line) preventing the interaction between the actuation button and the sliding bolt plate is shown.

Fig. 3a shows the actuation button 12 and the sliding bolt plate 11 in the starting position. The actuating button has a first rim 25 which is pressed against the cover of the housing 1 by the spring 13. The sliding bolt plate is tensioned by the drive mechanism 21, but the second rim of the actuating button 26 is prevented from abutting against the constriction 23. When the actuating button is pressed, the neck 27 between the first and second rims moves to the plane of the narrowing and the second rim moves out of the plane of the narrowing, and the first rotation of the sliding bolt plate is released until the pawl 24 hits the first rim 25 and the rotation is stopped.

Fig. 3b shows the actuation button 12 and the sliding bolt plate 11 in a position to stop after the first rotation. In this position, the pre-stressed flexible substrate has assumed a flat shape when relaxed and the introducer needle is fully inserted into the skin. When the actuation button is released, it is pushed back to the starting position and the first rim 25 moves above the plane of the pawl 24, thereby releasing a second rotation of the slide bolt plate until the end of the slot 22 of the slide bolt plate hits the second rim of the actuation button 26 and the rotation is stopped.

Fig. 3c shows the actuator button 12 and the sliding bolt plate 11 in the final position, which is stopped after the second rotation. In this position, not only the flexible substrate has assumed a flat shape, but also the guide needle is partially retracted, exposing the active surface of the diagnostic element to the interstitial fluid of the skin, and the control and measurement device is activated by a switch (not shown) actuated in the end position of the second rotation.

Various alternative embodiments will become apparent to those skilled in the art upon reading this specification. For example, partial retraction of the implantation mechanism and the introducer needle may be accomplished via a number of chemical, mechanical or electrical means. Furthermore, a wide variety of diagnostic elements and sensor arrays and control and measurement devices can be adapted to the apparatus. In addition, microdialysis systems can be constructed with a semipermeable dialysis membrane inserted into the skin with an introducer needle and the dialysis membrane exposed to subcutaneous fluid when the introducer needle is partially retracted. The dialysate solution can be pumped through a system with a micro-pump housed in the device, and the analyte in the dialysate can be analyzed online in the device, or sampled for later analysis.

Preferred sensors for analytes that fit well into the specifications of the present device can be constructed according to prior art procedures for electrochemical and optical sensors. The construction of miniaturized electrochemical and optical sensors is greatly improved by using matrix materials optimally suited for production by well established techniques, but such materials are often not suitable for direct implantation in the skin, for example because they are too flexible or may break if used directly to penetrate the skin. The introduction of such a sensor into the skin can only be achieved with an introducer needle and the partial retraction of the introducer needle greatly improves the design and handling of the patient. It allows to establish a permanent connection with the control and measurement device during manufacture: connections made by the patient, particularly after implantation, are problematic for miniaturized structures or are nearly impossible if conduction of very low electrical or other signals or fluids is necessary. The frequently used slit guide needles, which allow removal after implantation, cause significant tissue damage and limit miniaturization.

For the construction of electrochemical sensors, silicon or flexible substrates are ideal and technically well established, but for both a guide needle is required for implantation. The technology of flex-print for PCBs in electronic devices is directly used by covering parts of the active surface with suitable sensors for e.g. glucose, and the manufacture of flex-print is approaching a level making it well suited for the miniaturization of diagnostic components. To construct an optical sensor, a wide variety of methods may be optimally suited for direct determination of analytes or for indirect monitoring using suitable indicators. Such general methods may be associated with analyte-specific enzymatic reactions or with specific binding of receptors or antibodies. The present invention provides an easy solution to establish a permanent connection with the control and measurement means during manufacture, which is important for good performance of such miniaturized electrical or optical transmission fibers.

The invention has been described with reference to several specific and preferred embodiments, techniques, and applications. However, one of ordinary skill in the art will recognize that many variations and modifications and adaptations to the specific application and needs may be made while remaining within the spirit and scope of the present invention.

Claims (13)

1. A device for exposing an active surface of a diagnostic element to a bodily fluid for measuring the concentration of an analyte, the device comprising a hollow guide needle for subcutaneous insertion into a patient, the guide needle housing in its cavity an active surface of the diagnostic element and a connection wire to a measuring means of the diagnostic element, characterised by means for retracting the hollow guide needle relative to the diagnostic element to an extent sufficient to expose the active surface of the diagnostic element to a bodily fluid without disturbing a fixed connection between the active surface, the connection wire and the measuring means of the diagnostic element.

2. The apparatus of claim 1, including: a component having a flexible surface that ensures adhesion of the surface to the skin via an adhesive layer and a component having a rigid portion that holds one or more diagnostic elements contained within one or more introducer needles; and means for positioning the flexible surface relative to the introducer needle in such a manner that in a first position the introducer needle is concealed by the surface and in a second position the implantable portion of the introducer needle is exposed beyond the surface; and a mechanism to bring the surface from the first position to the second position.

3. The apparatus of claim 1, wherein the diagnostic element is fixedly positioned within the apparatus.

4. The apparatus of claim 1, comprising a sliding bolt mechanism configured such that insertion and retraction of the introducer needle into and from a portion of skin is continuously initiated by a release element.

5. The device of claim 4, wherein the release element that activates the sliding bolt mechanism is a button configured such that pressing an insertion mechanism that actuates the introducer needle into the skin and continuously releasing the button actuates partial retraction of the introducer needle and actuates a measurement.

6. The device of one of claims 1 to 4, wherein the active surface and/or the conductive part of the diagnostic element is flexible or has other properties that prevent safe placement into the skin without an introducer needle.

7. The device according to one of claims 1 to 5, wherein the active surface of the diagnostic element has a diameter of less than 250 μm and an implantation depth of 1 to 5mm and the guiding needle is retracted by 1 to 3 mm.

8. The device of one of claims 1 to 5, wherein the active surface of the diagnostic element comprises a sensor.

9. The device of claim 2, wherein the adhesive layer is for temporary wearing on a body, and the adhesive layer is secured on the flexible surface of the device by a reduced surface compared to an adhesive surface that adheres to skin.

10. The device according to claim 2, wherein the device is applied to the skin using a functional packaging which protects the release and actuation elements of the device from accidental activation and has a rim which presses the adhesive layer towards the skin and ensures its adhesion.

11. Apparatus according to one of claims 1 to 5, comprising control and measurement means for: a) monitoring the correct function of the device, b) converting the sensor signal into an analyte measurement value, c) storing, displaying and transmitting the analyte measurement value online or in batches, and d) issuing a warning signal if the analyte measurement value is not within a predefined range.

12. The apparatus of claim 11, wherein the apparatus further comprises means for delivering an infusion fluid into a patient, and the analyte measurement is used to control the delivery of the infusion fluid.

13. The device according to one of claims 1 to 5, wherein the device is composed of a reusable part comprising a reusable part of all control elements and of a disposable part comprising at least the active surface and the conductive part of the element for adhering to the skin, the guiding needle and the diagnostic element.