WO2011085845A1

WO2011085845A1 - Glucose sensor device having a porous micro-needle arrangement, corresponding manufacturing method and glucose measuring method

Info

Publication number: WO2011085845A1
Application number: PCT/EP2010/067683
Authority: WO
Inventors: Franz Laermer
Original assignee: Robert Bosch Gmbh
Priority date: 2010-01-13
Filing date: 2010-11-17
Publication date: 2011-07-21
Also published as: DE102010000843A1

Abstract

The invention relates to a glucose sensor device having a porous micro-needle arrangement, to a corresponding manufacturing method and to a glucose measuring method. The glucose sensor device (1; 1a) comprises a porous micro-needle arrangement (10) having at least one porous micro-needle (15a-d) and a glucose testing device (20, 25, 30, 35; 40, 45), which has a fluid receiving area (FA; FA') for receiving glucose-containing fluid and an electrical connection area (EA; EA') for connection to a glucose measuring apparatus (100). The porous micro-needle arrangement (10) is fitted to the fluid receiving area (FA; FA') in such a way that the glucose-containing fluid can be conducted from a surface of the porous micro-needle (15a-d) to the receiving area (FA; FA').

Description

description

title

Porous micro-needle assembly glucose sensor device, corresponding manufacturing method and glucose measurement method

State of the art

The present invention relates to a glucose sensor device with a porous microneedle array, a corresponding manufacturing method and a glucose measuring method.

Although applicable to any micromechanical devices, the present invention and its underlying background with respect to micromechanical devices in silicon technology will be explained.

Porous microneedle arrays, which consist for example of porous silicon, are on the one hand in the field of "Transdermal drug delivery" as an extension of drug patches, as a carrier of a vaccine or on the other hand also for the removal of body fluid (so-called intermediate tissue fluid - "Transdermal fluid") for Diagnosis and analysis of body parameters used.

DE 10 2006 028 781 A1 discloses a method for the production of porous micro-needles arranged on a silicon substrate in an array for the transdermal administration of medicaments. The method includes forming a microneedle array having a plurality of microneedles on the front side of a semiconductor substrate rising from a support region of the semiconductor substrate, and partially porosifying the semiconductor substrate to form porous microneedles, the porosification starting from the front side of the semiconductor substrate and a porous one Reservoir is formed by the cavities inside the structures.

Another method for producing a porous microneedle assembly is known from CN 100998901 A. EP 1 820 441 A1 discloses a micro needle assembly with sensor based on attenuated total reflection. The sensor includes a needle assembly with hollow needles, the proximal end of the needles terminating in a chamber in which body fluid entering through the distal end of the needle can be collected. A window, which is at least partially permeable to infrared radiation, comes into direct contact with the chamber.

EP 1 894 525 A1 discloses a plastic packaging for hydrophilically coated medical instruments intended to ensure the hydrophilicity of the enclosed instrument over a long period of time.

DE 10 2006 025 864 A1 discloses a mobile device with a device for measuring electrical potentials in a patient with at least one needle-like extension in order to penetrate into an uppermost skin layer of the patient.

Diabetics need to regularly determine their blood glucose levels. There are numerous products from various manufacturers, which have in common that initially with a lancing device a stab through the skin is usually carried out on the fingertip and the exiting blood drop is then absorbed and evaluated by a plugged into a meter glucose test strip. The glucose measuring strip usually generates an electric current whose value depends on the glucose concentration in the absorbed drop of blood and which is determined, displayed and stored by the measuring device. This known method of determining the blood glucose value thus provides for two separate processes: stinging and measuring. In particular, the constant stinging is painful for the diabetic and causes permanent tissue scarring and neuropathy, so the diabetic after some time often no longer find suitable places on the finger berries and "dodging" on other parts of the body. Also, the handling of blood is uncomfortable and associated with infection risks for both the patient and his environment. Used and blood-contacting components should be disposed of as "bio-hazard". This is especially true in terms of infection risks for HIV and hepatitis. Advantages of the invention

The glucose sensor device with a porous microneedle assembly defined in claim 1 and the corresponding manufacturing method according to claim 10 and the glucose measuring method and system according to claim 15 have the advantage that the glucose measurement can be carried out with a single procedure which causes no pain. leaves no scarring and is not accompanied by leakage of blood. For this purpose, the measuring technique known from the prior art is coupled with a porous microneedle arrangement. To determine the glucose value, it is not blood but the transdermal fluid under the surface of the skin, i. H. under the stratum corneum. Since the penetration depth of the microneedle assembly is well defined by its height and is so low that neither nerves nor blood vessels are injured, the favorable properties of "painless" and "bloodless" can be achieved and thus also reduce the risk of infection in a significant way. The penetration depth of the microneedles ends design-controlled above the so-called basement membrane, below which then blood vessels and nerves.

The idea on which the present invention is based is to combine the measurement technology established with glucose measurement strips with a porous micro-needle arrangement. The measuring technique known from the prior art comprises a sequence of layers and contacts, which are usually applied by printing techniques on ceramic supports and / or plastic supports, which are also referred to as glucose measuring strips. These gauges are connected to a glucose meter for evaluation, which is done by simply inserting it into the gage interface. The features listed in the dependent claims relate to advantageous developments and improvements of the subject matter of the invention.

According to a preferred development, the glucose test device is a glucose measuring strip onto which the porous microneedle arrangement is applied, for example adhesively bonded. The advantage of this latter concept is the complete decoupling of the manufacturing processes for the microneedle assembly and the glucose metering strips, both of which are processed independently of each other and assembled at the end of the manufacturing process. Another advantage is that the production of the glucose gauges can be substantially unchanged and in particular on the same systems at the same manufacturers as in the current state of the art, only extended by the assembly step of the microneedle assemblies 10 on the Glucose test strips just before the end of the production process of the glucose test strips.

This allows a process flow in which the manufacturer of the glucose test strips leads his process with his know-how in the usual way and last the

The micro-needle arrays of its supplier, who controls the silicon technologies of porosity and microneedle production through plasma etching and has the necessary know-how, has expanded. The extent of the sensitive range of today's glucose measuring strips is in the order of 1 mm ² to a few mm ² , which is also an ideal size for microneedle arrays 10, results in a high Wafernutzen and thus results in very low cost.

According to a further preferred development, the glucose test device comprises a signal generating device, which is placed on the back of the porous microneedle array, a contact plate and a contact arrangement, wherein the signal generating device is connected via the contact arrangement with the contact plate. This enables complete fabrication of the wafer level measurement systems, at the end of which the glucose sensor devices are singulated. According to a further preferred development, the porous microneedle assembly has a removable protective cap, wherein the protective cap e.g. a pull-tab for removing the protective cap or wherein e.g. a gap for attaching a tool for removing the protective cap is provided between the protective cap and the porous microneedle assembly. This enables effective protection of the sensitive microneedles from their manufacture to application on the skin.

According to a further preferred refinement, a trench structure is provided on the rear side of the porous microneedle array or a trench structure and / or passage openings are provided on the upper side of the glucose measuring strip in the fluid accommodating area. This allows for efficient removal of air in the micropores during the advance of the transdermal fluid to the signal generation plane.

According to a further preferred refinement, an autonomous wireless transmitting device is provided for transmitting glucose measurement data to a glucose meter at the glucose test device or connected thereto. This allows a continuous glucose test without the need to always carry a glucose meter. This meter can be provided as a stationary device or as a dedicated mobile device or even integrated into an existing mobile device, such as a mobile phone or PDA or as an application in the iPhone ®.

drawings

Embodiments of the invention are illustrated in the drawings and explained in more detail in the following description.

Show it:

1 shows a glucose sensor device according to a first embodiment of the present invention;

FIG. 2 shows a glucose sensor device according to a second embodiment of the present invention; FIG.

3 shows a glucose measuring system according to a third embodiment of the present invention, which uses the glucose sensor device according to FIG. 1 or 2;

4 shows a glucose measuring system according to a fourth embodiment of the present invention, which uses the glucose sensor device according to FIG. 1 or 2;

5 shows a glucose sensor device according to a fifth embodiment of the present invention;

6 shows a glucose sensor device according to a sixth embodiment of the present invention;

7a, b show a glucose sensor device according to a seventh embodiment of the present invention, FIG. 7a in a bottom plan view of the microneedle assembly, and FIG. 7b in a partial cross-section through the microneedle assembly along the line AA; and

8 shows a glucose sensor device according to an eighth embodiment of the present invention. Description of exemplary embodiments

In the figures, like reference numerals designate the same or functionally identical elements.

Fig. 1 shows a glucose sensor device according to a first embodiment of the present invention.

In Fig. 1, reference numeral 1 denotes a glucose sensor device according to the first embodiment of the present invention which comprises a porous microneedle array 10 which in turn comprises a plurality of porous microneedles 15a-15d rising from the front side VS of a porous support portion 12. Reference numeral 11 designates pores which pass through the carrier region 12 from the rear side RS to the front side VS and, based thereon, the microneedles 15a-15d and thus form a multiplicity of fluid channels.

In this first embodiment of the invention, the complete layer system of the signal generating device 20 is printed with its known per se and glucose-determining layer structure on the back of a porous silicon wafer, so that the porous microneedle assembly 10 is mounted on a fluid receiving area FA of the signal generating means 20. The known layer and contact structure for glucose value determination (referred to here as signal generation level 20) contains, in addition to printed conductors, also electrochemically active layers or other measuring elements in order to "flow" the glucose component or otherwise convert it into a signal.

The wafer (not shown) either carries the plurality of microneedle arrays 10 on its front side during printing or, after being printed, is patterned on the front side by plasma etching to the microneedle arrays 10. After separation, the individual measuring elements ME with their respective

Micro-needle assembly 15a - 15d and located on the back RS signal generating device 20 are glued to a respective contact plate 30 with a corresponding contact assembly 25, which in turn can be inserted and electrically contacted in a glucose meter of a commercially available type. About the contact plate 30 and the contact assembly 25 and provided in the contact plate 30 traces 35 in an electrical connection area EA thus takes place the electrical connection of the measuring elements ME and the electrical connection to the glucose meter (see Fig. 3 and 4).

The wafer must be completely through-porosified from front to back before printing with the layers and contacts of the signal generator 20, since the porosification takes place in aggressive hydrofluoric acid solution which must not come into contact with the layers of the signal generator 20.

Due to the porous structure is achieved that for the transdermal fluid

Passing from the microneedles 15a - 15d through the carrier region 12 to the back of the signal generating device 20 supporting RS is possible.

In addition, porosification is necessary to produce a biocompatible surface and structure of silicon that does not result in rejection reactions, encapsulation, or inflammation in the skin and also ensures that any broken needle parts dissolve relatively quickly in the skin to harmless silica, without causing irritation.

In terms of process technology, different production variants are available for the glucose sensor device shown in FIG. 1 according to a first embodiment of the present invention.

Thus, the microneedles can first be prepared on the wafer front side by plasma etching and then porosified the wafer. This can take place without current or particularly advantageously under the energization of the wafer, since the current leads to more strongly directed pore structures from the wafer front side to the wafer back side. In the latter case, however, the majority of the pores 11 do not generally extend to the wafer back side, so that subsequently a considerable layer thickness has to be removed from the wafer back side until it reaches sufficiently porous silicon in the bulk of the wafer. The latter can be done with appropriate protection of the sensitive wafer front that carries the microneedles, for example, by grinding or wet etching or dry etching of the wafer back. Only when the wafer back side is massively porous, the layer system of the signal generating device 20 can be applied for determination of the glucose value. The protection of the wafer front side with its sensitive structures is critical here, above all because the spectrum of usable chemicals for the removal of protective layers of the front side is limited by the layer system of the wafer backside. Alternatively, the porosification of the wafer is started, which in turn can take place without current or particularly advantageously under the current supply of the wafer. In this process variant as well, the majority of the pores in the electrochemical porosification generally do not reach the backside of the wafer, so that the back of the wafer has to be back ground, backdrawn or dry etched back until the reverse side has been propelled into the silicon of high porosity in the bulk of the wafer. Thereafter, the layer system of the signal generating device 20 is applied to the wafer backside for glucose measurement. The advantage of this process variant is that by this time a robust wafer without sensitive front side structures can be traded through all process steps. Only after completion of all backside processes the microneedle arrays 10 are generated by plasma etching on the front side. Considering this is the fact that porous silicon absorbs the toxic plasma chemistry of the etching plasma in the form of deposits from the etching plasma, which must subsequently be removed very carefully. This is done by a sequence of dry chemical steps, for example 0 ₂ plasma and / or ozone, wet chemical cleaning steps, z. B. in H ₂ 0 ₂ and then annealing in oxygen or ozone at elevated temperature. By means of these measures, it is further advantageously achieved that the internal structure of the porous silicon is oxidized and hydrophilized, which is advantageous for later use, as will be explained later. A particular advantage is the property of porous silicon to be electrically insulating. Thus, no adulteration of currents generated by the applied layer system occurs during later use for the measurement of glucose concentrations, without the need for additional insulation measures in the form of applied insulating layers.

Fig. 2 shows a glucose sensor device according to a second embodiment of the present invention.

In contrast to the above first embodiment, in the glucose sensor apparatus 1 a according to the second embodiment, the porous microneedle array 10 is located on a fluid receiving area FA 'of the surface O of a glucose measuring strip 40 which is known per se glued. Reference symbol EA 'designates a corresponding electrical connection region of the measuring strip 40 with conductor tracks 45 provided there.

This alternative concept therefore envisages combining a glucose measuring strip of essentially contemporary design with a microneedle arrangement 10, in that after application of the layer system for determination of glucose to a conventional ceramic carrier or plastic carrier, the microneedle arrangement 10 is glued directly onto the layer system or fixed in another way suitable. This can be done for example by means of so-called pick-and-place techniques by industrial robots or machines, optionally supported by electronic image processing, so that each a porous microneedle array 10 is placed directly on the fluid receiving area F of each glucose measuring strip 40 and properly fixed before the carrier is separated into glucose sensor devices 1 a. Here, too, it is again advantageous that porous silicon has an electrically insulating effect and can be applied directly to the layers of the measuring strip 40 without additional electrical insulation measures in the form of additionally applied insulation layers. After separation by sawing the support material, these are optionally dried, calibrated and then sold in dry packaged form.

By separating the production of the glucose test strips 40 and the microneedle arrays 10 to be applied thereon, the options for the

Production of the microneedle arrangements 10, since it is not necessary to take into account a wafer backside carrying a layer system of a signal-generating device 20. In particular, the wafer front side can advantageously first be patterned into microneedle arrangements and subsequently be porosified, and finally the wafer backside can be removed until it has been advanced to sufficiently porous silicon in the bulk of the wafer. The required protection of the sensitive wafer front side, which carries the microneedles 15a-15d, is not subject to any limiting boundary conditions of a layer system on the wafer back, so that a much greater selection of protective measures and their subsequent removal, such as detachment of polymer materials by aggressive chemicals, etc .. can be taken. Furthermore, it is possible to metallize the wafer back side before the production of the porous silicon or the porosification and via this metal, for. Aluminum optionally combined with an additional metal layer or laminated metal foil, to contact. This makes it possible to porosify through to the back of the silicon wafer. The metallization must then be removed wet-chemically, that is, etched off and / or optionally removed again by using appropriate solvents or simply stripped off.

It is particularly advantageous if it is assumed that the wafer is completely through-porosified, which has been porosified electrochemically or electrolessly, and the reverse side of which has been thinned back by grinding wet or dry etching, so that sufficiently porous layers in the bulk of the silicon wafer have been achieved. Only then is the wafer front side patterned by plasma etching into microneedle arrays 10, which results in a coating of the internal structure of the porous silicon with toxic deposits from the plasma chemistry of the etching plasma. As said, these toxic deposits must be carefully removed by plasma treatment in oxygen or ozone combined with subsequent wet chemistry of, for example, H ₂ O ₂ or H ₂ O ₂ combined with NH ₃ or H ₂ O ₂ combined with HCl and a Entendpanner (surfactant) or HN0 ₃ and a relaxant (surfactant) can be done. In this cleaning, a variety of chemicals can be used, since no consideration has to be taken of a layer system on the back of the wafer. In particular, in addition to the cleaning effect, particularly good hydrophilic properties of the internal structure of the porous silicon can be achieved, which is advantageous for the application. The advantage of this process variant is again that sensitive structures are created on the wafer front just shortly before the end of the process and expensive protective measures for the front can be dispensed with.

A further possibility for achieving a hydrophilization consists in a Präoxidi- dation at high temperatures of 400 ° C to 900 ° C, more preferably in the range of 500 ° C to 800 ° C in oxygen, oxygen-containing atmosphere, in ozone or ozone-containing atmosphere , in water vapor, in water vapor / oxygen or water vapor-ozone mixtures or in an atmosphere of nitrogen oxides, nitric acid, hydrogen peroxide or other oxidizing moist gases. At temperatures in the range of 500 ° C to 800 ° C, the internal structure of the porous silicon does not yet collapse, but on the other hand, a very intensive oxidation of the inner surface of the silicon pores occurs, and the higher the temperature, the better

Tolerable limits, which is advantageous for the desired hydrophilization. In a further preferred embodiment, the temperature during this Präoxidati- on starting from an initial value of z. B. 400 ° C, more preferably of z. B. 500 ° C, slowly raced up to a final value of z. B. 900 ° C, particularly preferably z. B. 800 ° C to take advantage of the progressing oxidation stabilization of the internal structure of the porous silicon for further increase in temperature to achieve higher degree of oxidation and thus stabilization, so that an advantageous for the further oxidation increasingly higher temperature without

Damage is tolerated by the internal porous silicon structure. For this purpose, either the oven used for the oxidation can be slowly up-regulated in its temperature on the introduced heating power, z. B. from 500 ° C to 800 ° C over a period of z. B. 10 to 60 min., Preferably 30 min., Or one uses a zone heating with a low temperature at the beginning of the heating zone and a high

Temperature at the end of the heating zone, with the wafers slowly from the beginning to the

End of the heating zone, which may be designed as a tubular reactor or tunnel reactor or tunnel furnace, transported and thereby pass through the temperature ramp spatially. This transport process can be for a wafer z. B. each half

Take hour and in a continuous furnace continuously, d. H. Waferboot take place behind WABERBOOT.

In any case, a careful pre-oxidation of the porous silicon structure promotes the inner hydrophilicity and thus the subsequent absorption of the transdermal fluid from the skin and the transport to the actual measuring system. FIG. 3 shows a glucose measuring system according to a third embodiment of the present invention using the glucose sensor device of FIG. 1 or 2. FIG.

The glucose measuring system has a glucose sensor device 1 or 1 a according to FIG. 1 or 2, which can be inserted into a receiving slot SL of a commercially available glucose meter 100. The glucose meter 100 has u. a. a display device 1 10 for displaying the determined glucose value.

Regardless of whether the signal generating device 20 is integrated on the back of a porous microneedle array 10 or whether a porous microneedle array 10 is fixed on a commercially available glucose measuring strip 40, the glucose sensor device 1 or 1 a according to FIG. 1 or 2 to determine the glucose value mung in a receiving slot SL of a commercially available glucose meter 100 inserted.

Following this, the microneedle arrangement 10 of the glucose sensor device 1 or 1a is pressed into the skin, which, due to the small height of the microneedles 15a-15d, is 50 to 200 .mu.m, preferably 100 to 150 .mu.m, painless and bloodless because at these depths in the skin still no nerves and no blood vessels occur. This is particularly important because the measurement in the transdermal fluid should be done and not be falsified by an ingress of blood from possibly injured blood vessels. At this point, the high precision and reproducibility of microtechnology in silicon pays off, which ensures precisely defined microneedle heights and thus precisely defined penetration depths. Immediately upon contact of the porous needle with the transdermal fluid, the latter is absorbed by the porous structure, for which the pronounced hydrophilic properties of the porous silicon are responsible.

Therefore, hydrophilization of the porous silicon as described above is important to the functioning of the glucose sensor devices 1 and 1a, respectively. The microneedles 15a-15d are left in the skin until sufficient transdermal fluid has been absorbed and transported through the carrier region 12 to the actual measuring system, ie either signal-generating device 20 or measuring strip 40, so that the measurement is carried out there after a few seconds can be. Unlike using a lancing device, piercing when using a microneedle assembly is now no longer a very fast event, but a process that continues for many seconds over the entire measuring process. Since the process is now completely painless and bloodless, eliminating any need for a high speed. The affected patient presses the measuring strip with the microneedle assembly against the skin until it receives a measurement result. This will take a few seconds, during which the affected patient feels no pain and no unpleasant side effects occur. Scarring or neuropathies are also not expected due to the low penetration depths. As a result, painless puncture and measurement are combined in one step, which represents a significant improvement in the glucose value determination compared to the current state of the art. Since the glucose value of the transdermal fluid deviates from that of the blood and in particular involves a time delay of up to 30 minutes compared with the blood level, the glucose meters 100 must be correspondingly corrected or calibrated for transdermal fluid. The improved comfort and quality of life more than outweighs the time delay over the blood value, since the time difference for most diabetics is insignificant for control or measurement-derived therapy.

It is even possible to track the glucose level in the transdermal fluid for a long time by simply leaving a microneedle array and attached measuring system in the skin for a correspondingly long time. In practice, the chemistry of a glucose measuring strip consumes only hours to days, depending on the design of the system, so that in principle even a continuous monitoring of the glucose level over a long time is possible. This is further countered by the fact that porous silicon is biocompatible and no rejection reactions, encapsulation or inflammatory processes in the skin over a longer period of time

Episode has. For this purpose, the measuring system with the microneedle assembly is pressed into the skin and z. B. fixed by means of a plaster there. The measuring system is therefore in contact with the transdermal fluid under the stratum corneum via the porous microneedles for a long time.

FIG. 4 shows a glucose measuring system according to a fourth embodiment of the present invention using the glucose sensor device of FIG. 1 or 2. FIG.

In the measuring system shown in FIG. 4, the measurement results are continuously fed wirelessly to the glucose meter 100a. For this purpose, the glucose sensor device 1 or 1a according to FIG. 1 or 2 has a corresponding battery-operated transmitting device 80 or is connected to such a transmitting device which continuously communicates data information bearing the reference symbol SS to a receiving device 85 provided in the measuring device 100a. The technique of wireless transmission of measurement data from a measurement system to peripheral devices is well known in the prior art and will not be further detailed here. For example, you can use Bluetooth or Zigbee interfaces. Via the porous silicon and the mass transfer through the porous structure, the measuring system remains coupled to the transdermal fluid and thus undergoes the same

Glucose level fluctuations over a long period of time. Unlike the present technology of separate puncturing and measuring, a continuous connection of the measuring system to the skin and the glucose meter and thus monitoring over a longer period of time is possible. can also be used in a telemedical application. Fig. 5 shows a glucose sensor device according to a fifth embodiment of the present invention, and Fig. 6 shows a glucose sensor device according to a sixth embodiment of the present invention.

The fifth and sixth embodiments relate to the handling protection for the sensitive microneedles once they have been made by plasma etching.

Microneedles 15a-15d are pointed, filigree structures made of a brittle material, for example porous silicon, which can subsequently be easily damaged as a result. For example, the microneedles 15a-15d can break off completely or in part simply by mechanical action, in particular the sensitive tips can be damaged.

In order to largely protect the microneedles 15a-15d, it is proposed, as soon as possible after their manufacture, ie as soon as the fabrication process permits, to cap them by means of caps 50, preferably by means of plastic caps. These

Caps 50 made of plastic can for example be produced separately by means of injection molding or hot stamping processes and preferably glued as a separate wafer composite as a unit onto the wafer with the microneedle arrays 10 via an adhesive joint K. By adjusting the two wafers to each other while a micro needle assembly 10 is combined with a cap 50 each. For example, one suitable time for capping in the fabrication process is the condition in which the microneedles 15a-15d are plasma etched and porosified and hydrophilized. As soon as the caps 50 or the wafer with the caps 50 are glued on, the wafer can be further processed relatively danger-free with the microneedle arrangements 10. For example, it is then easily possible to grind back the wafer with the microneedle arrays from the rear side and, for this purpose, to fix it on a grinding carrier device on the front side. which presses it back against the actual grinding wheel or the grinding medium. Furthermore, the wafer on its front side is largely protected against the influence of the sawing process during sawing from the front or the back side, ie against mechanical effects of particles due to sawing wear.

Preferably, the plastic cap wafer is diced with the singulation to microneedle arrays simultaneously to individual caps per microneedle array. Also, the subsequent mounting and bonding of the porous microneedle arrays to the glucose measurement strips with pick-and-place or similar mechanical gripping and assembly steps, the subsequent sawing of the glucose strip carrier material into individual glucose measuring strips, handling and packaging of the glucose measuring strips in suitable containers, the Trade route to the customer, unpacking and handling on the customer side, all this can be done advantageously with firmly mounted cap on the glucose test system and thus protected microneedle assembly.

Only immediately before a glucose value determination, the customer aborts the plastic cap 50, for example, in a predetermined breaking point in the material or in the glue joint by a starting point 51 for a lever tool 52 (FIG. 5) or with an attached pull tab 53 (FIG one of many other alternatives.

It is advantageous that the microneedle arrays 10 remain in a protected state from the said suitable point in the manufacturing process to the end application at the customer under the glued plastic cap and are safe from damage. The requirements for the plastic and the bonding are comparatively low. Hermeticity is not required, material expansion of the plastic cap relative to the porous silicon or silicon can be absorbed by the adhesive joint K. The adhesive only has to ensure a sufficiently strong but not too strong connection, because in the end the customer should have the

Cap 50 can lose weight. Particularly advantageous is the option of a starting point for a lever tool 52 to be implemented, which is supplied with the glucose test systems, for example, a lever for shearing the plastic caps on an attached groove or marking each after insertion into the actual glucose meter and immediately before piercing the skin.

7a, b show a glucose sensor device according to a seventh embodiment of the present invention, in particular FIG. 7a in a top view of the microneedle device tion and Fig. 7b in partial cross section through the microneedle array along the line AA '.

In general, it must be ensured that when the transdermal fluid is absorbed, the air displaced in the porous silicon can escape without trapping air bubbles, which would stop the further penetration of the transdermal fluid in the affected area, so that it stops locally could get to the measuring system. This can be achieved for example by a grid of depressions 12a, 12b on the rear side RS of the carrier region 12 of the microneedle assembly 10, which each reach a plurality of pores 11 and extend to the edge of the carrier region 12, so that the air can be discharged there is. One way of applying such trench gratings 12a, 12b in the microneedle arrays 10, for example, provides a sawing process from the wafer backside, in which the saw blade completely cuts through the silicon thickness in the sawing areas, but only cuts with a small depth of cut are made close to the surface in between. The respective depth of cut can be flexibly programmed with the commercially available wafer saws, so that this approach can be implemented easily and inexpensively. In addition, numerous possibilities are known for milling, scoring, etching, laser machining into a silicon surface under low precision requirements, etc. Since the lattice-shaped groove structures 12a, 12b merely provide an escape for the displaced air and do not fulfill any mechanical function need the required precision at this point is relatively low, which allows various alternative solutions.

Fig. 8 shows a glucose sensor device according to an eighth embodiment of the present invention.

In this embodiment, from a microneedle array 10 adhered to a glucose metering strip 40, the trenching structure that provides the displaced air with an opportunity to escape may also be applied to the glucose metering strip 40. The escape can take place laterally through a groove structure with depressions 13a-13e, or one additionally creates perforation openings 14 through the glucose measuring strip 40, or one combines both options.

Claims

claims

1 . A glucose sensor device (1; 1 a) comprising: a porous microneedle assembly (10) having at least one porous microneedle (15a-d); a glucose test device (20, 25, 30, 35, 40, 45), which has a fluid intake area (FA; FA ') for receiving glucose-containing fluid and an electrical connection area (EA; EA') for connection to a glucose Measuring device (100); wherein the porous microneedle assembly (10) is mounted on the fluid receiving portion (FA; FA) such that the glucose-containing fluid is conductive from a surface of the porous microneedle (15a-d) to the receiving portion (FA; FA).

A glucose sensor device (1; 1 a) according to claim 1, wherein the glucose test device (20, 25, 30, 35, 40, 45) is a glucose measuring strip (40, 45) on which the porous microneedle assembly (10) 10) is applied.

A glucose sensor device (1; 1 a) according to claim 1, wherein the glucose test device (20, 25, 30, 35, 40, 45) has signal generating means (20) mounted on the back side of the porous microneedle array (10) is, a contact plate (30) and a contact arrangement (25), wherein the signal generating means (20) via the contact arrangement (25) with the contact plate (30) is connected.

The glucose sensor device (1; 1 a) of any one of claims 1 to 3, wherein the porous microneedle assembly (10) comprises a removable protective cap (50).

The glucose sensor device (1; 1 a) according to claim 4, wherein the protective cap (50) has a pull-tab (53) for removing the protective cap (50).

A glucose sensor device (1; 1 a) according to claim 4, wherein a gap (51) for attaching a tool (52) for removing the protective cap (50) is provided between the protective cap (50) and the porous microneedle assembly (10) ,

7. glucose sensor device (1; 1 a) according to any one of claims 1 to 6, wherein on the back of the porous microneedle assembly (10) a trench structure (12a, 12b) is provided.

8. glucose sensor device (1; 1 a) according to claim 2, wherein on the upper side (O) of the glucose measuring strip (40) in the fluid receiving area (FA ') a trench structure (13a-d) and / or passage openings ( 14) are provided.

9. glucose sensor device (1; 1 a) according to one of claims 1 to 8, wherein a wireless transmitting device (80) for transmitting glucose measurement data to a glucose meter (100a) on the glucose test device (20, 25, 30, 35, 40, 45) is provided or connected thereto.

10. A manufacturing method of a glucose sensor device comprising the steps of:

Forming a porous microneedle array (10) with at least one porous microneedle (15a-d); Attaching the porous microneedle assembly (10) to at least one porous microneedle (15a-d) on glucose testing equipment (20, 25, 30, 35, 40, 45) having a fluid receiving area (FA; FA ') for receiving glucose-containing fluid and an electrical connection area (EA; EA) for connection to a glucose meter (100); wherein the porous microneedle assembly (10) is mounted on the fluid receiving area (FA; FA) such that the glucose-containing fluid is conductive from a surface of the porous microneedle (15a-d) to the receiving area (FA; FA ').

1 1. The method of claim 10, wherein the glucose assay device (20, 25, 30, 35, 40, 45) is a glucose sensing strip (40, 45) to which the porous microneedle assembly (10) is applied.

12. The method according to claim 10, wherein the glucose test device (20, 25, 30, 35, 40, 45) comprises a signal generating device (20) which is applied to the rear side of the porous microneedle array (10), a contact plate (30 ) and a contact arrangement (25), wherein the signal generating device (20) is mounted on the contact plate (30) via the contact arrangement (25).

13. The method of claim 1 1, wherein a wafer is prepared with a plurality of porous microneedle arrays (10) and mounted on the glucose test device (20, 25, 30, 35, 40, 45) after singulating the microneedle arrays (10 ) by a pick-and-place technique.

14. The method of claim 12, wherein a wafer is prepared with a plurality of porous microneedle arrays (10) and applying a plurality of signal generating means (20) of the glucose test device (20, 25, 30, 35, 40, 45) on the Waferrückseite before a separation of the microneedle arrays (10) takes place.

15. A glucose measurement method using a glucose sensor device according to claim 1, wherein at the glucose test device (20, 25, 30, 35, 40, 45) a transmitting device (80) for wirelessly transmitting glucose measurement data is provided this is connected, wherein the transmitted glucose measurement data from a receiving device (85) of a glucose meter (100a) are received and then evaluated in the glucose meter (100a) and optionally stored and / or forwarded.