阅读说明：本技术 用于诊断的皮肤贴片 (Skin patch for diagnosis ) 是由 T·舍斯特 于 2018-12-13 设计创作，主要内容包括：本发明提供一种医疗器械,包括皮肤附着表面(3)和蒸发层(9),以及从所述皮肤附着表面(3)延伸的至少一个空心微针(4),所述医疗器械(1)还包括流道(6),用于分析体液的分析单元(8),和蒸发层(9),其中所述流道(6)布置为将流体从所述微针(4)输送到所述分析单元(8)并从所述分析单元(8)输送到所述蒸发层(9),使得所述流道(6)能够将流体排放到所述蒸发层(9)中。(The invention provides a medical device comprising a skin attachment surface (3) and an evaporation layer (9), and at least one hollow microneedle (4) extending from the skin attachment surface (3), the medical device (1) further comprising a flow channel (6), an analysis unit (8) for analyzing a body fluid, and an evaporation layer (9), wherein the flow channel (6) is arranged to transport fluid from the microneedle (4) to the analysis unit (8) and from the analysis unit (8) to the evaporation layer (9) such that the flow channel (6) is capable of discharging fluid into the evaporation layer (9).)

1. A medical device comprising an attachment surface (3) and an evaporation layer (9), and at least one hollow microneedle (4) extending from the attachment surface (3), the medical device (1) further comprising a flow channel (6), an analysis unit (8) for analyzing a body fluid, and an evaporation layer (9), wherein the flow channel (6) is arranged to transport fluid from the microneedle (4) to the analysis unit (8) and from the analysis unit (8) to the evaporation layer (9), such that the flow channel (6) is capable of discharging fluid into the evaporation layer (9).

2. The medical device of claim 1, wherein the medical device comprises a body, and wherein the at least one microneedle extends from the body and the analysis unit is included in the body.

3. The medical device of claim 1 or 2, wherein the transport of fluid through the medical device is drivable by the evaporation layer.

4. The medical device of claim 3, wherein the flow of fluid is initiated by a disposable pump.

5. The medical device of any one of claims 1-4, wherein the medical device includes at least one heat-generating electronic unit, and the evaporation layer is disposed in contact with the at least one heat-generating electronic unit.

6. The medical device of any one of claims 1-5, comprising a thermally conductive element disposed between the attachment surface and the evaporation layer.

7. The medical instrument according to claim 6, wherein the heat conducting element is arranged between the evaporation layer and a heat generating electronic unit.

8. The medical device of any one of claims 5 to 7, wherein the heat-generating electronic unit or the thermally conductive element is provided with at least one surface area increasing element.

9. The medical device of any one of claims 1-8, wherein the evaporation layer has antibacterial activity.

10. The medical device of any one of claims 1-9, wherein the evaporation layer is removable from the medical device and replaceable by another evaporation layer.

11. The medical device of any one of claims 1 to 10, comprising a skin attachment layer comprising the attachment surface, wherein the skin attachment layer is removable from the medical device and replaceable by another skin attachment layer.

12. The medical device of any one of claims 1-11, wherein the skin attachment layer comprises the at least one microneedle.

13. An evaporation layer for attachment to the medical device of claim 11.

14. A skin attachment layer for attachment to a medical device according to claim 10 or 12.

15. The skin attachment layer of claim 14, which comprises at least one microneedle.

16. A method of analyzing a body fluid, comprising the steps of: attaching a device according to any one of claims 1 to 12 to the skin of a user; collecting bodily fluid from a user using the at least one microneedle; analyzing the body fluid using the analysis unit; allowing at least a portion of the fluid to be absorbed by the evaporation layer; and allowing at least a portion of the fluid to evaporate from the evaporation layer.

Technical Field

The present invention relates to a medical device for attachment to skin, the device comprising at least one hollow microneedle for measuring an analyte, such as glucose, in a fluid, such as interstitial fluid.

Background

Diabetics need to measure glucose concentration in the blood periodically, sometimes several times a day. Today, this is usually done by the patient piercing his own skin to produce a drop of blood which is then analyzed. Blood was collected by a glucose measuring stick inserted into the portable glucose measuring device. This process is performed every time blood glucose is measured. This is cumbersome because the patient needs to carry the device and test stick, must remember to perform the test, and must puncture his or her skin each time blood glucose is measured. This results in some patients reluctant to measure blood glucose frequently. This can be very dangerous for the patient.

The Abbot FreeStyle library provides a solution to this problem because it provides a skin patch with a needle that is inserted into the skin and allows continuous blood glucose measurements to be taken. A blood glucose monitoring system (FreeStyle library) patch may analyze blood glucose and may wirelessly transmit the measurements to a portable device. However, this product causes some discomfort due to the needle length of about 5 mm.

In addition to blood glucose, there are many different analytes that may benefit from continuous measurement, such as hormones or other signaling molecules, toxins, infection indicators, and the like.

WO90333898 discloses a device for sampling fluid from a user, wherein the fluid is collected in a closed chamber having a limited space, making the device unsuitable for collecting large amounts of fluid.

Wentrelli (Ventrelli) et al (Adv Helthcar Mater, 2015, DOI: 10.1002/adhm.201500450) describe various microneedle arrays that are analyzed inside microneedles. The disadvantage is that the analytical electrode has to be miniaturized, which makes it difficult to manufacture.

Accordingly, there is a need for a more comfortable device for measuring analytes in a patient that can be used for a long period of time.

Disclosure of Invention

In a first aspect of the invention, a medical device is provided comprising a skin attachment surface and an absorbent layer, preferably an evaporation layer, and at least one hollow microneedle extending from the skin attachment surface, the medical device further comprising a flow channel, an analysis unit for analyzing body fluids and an evaporation layer, wherein the flow channel is arranged to transport fluid from the microneedle to the analysis unit and from the analysis unit to the evaporation layer such that the flow channel can release fluid to the evaporation layer.

One advantage of this device is that the evaporation layer enables the device to handle large volumes of fluid. Therefore, the device can be used for a long time. Furthermore, the analysis unit does not have to be miniaturized to a large extent.

The device may comprise a pump unit for transferring fluid from the microneedles to the evaporation layer. The pump helps to create a flow from the microneedles to the evaporation layer.

In various embodiments, fluid transport through the medical device is driven by the evaporation layer. The flow of fluid may then be initiated by the disposable pump.

The device preferably comprises a body, wherein said analysis unit is comprised in said body. At least one microneedle extends from the body. Therefore, the analysis unit is not included in the microneedle. This has the advantage that space in the body is used for the analysis unit, rather than placing a part of the analysis unit in the hollow microneedle.

The evaporation rate from the evaporation layer may be equal to or higher than the flow rate in the flow channel, especially when the flow of fluid in the device is caused by evaporation.

The medical device may comprise at least one heat-generating electronic unit, wherein the evaporation layer is arranged in contact with the at least one heat-generating electronic unit. This has the advantage of increasing the evaporation capacity of the evaporation layer. The device may comprise a heat conducting element arranged between said attachment surface and said evaporation layer. This has the advantage of conducting heat away from the user's body, increasing the evaporation capacity of the evaporation layer. The heat conducting element may be arranged between the evaporation layer and the heat generating electronic unit.

The heat generating electronic unit or the heat conducting element may be provided with at least one surface area increasing element, such as at least one heat dissipating fin.

The evaporation layer has antibacterial activity to prevent propagation of bacteria and the like. The fluid handling of the evaporation layer may be based mainly on absorption and retention of fluids, wherein the evaporation effect is less important.

In selected embodiments, the vaporization layer may be removed from the medical device and replaced with another vaporization layer. In one embodiment, the device comprises a skin attachment layer comprising an attachment layer, wherein the skin attachment layer is removable from the medical device and replaceable by another skin attachment layer. The skin attachment layer may comprise at least one microneedle. Thus, in one embodiment, the skin attachment layer and the at least one microneedle can be removed from the medical device as a unit and replaced with another attachment layer. This allows the reuse of expensive components of the device. Thus, the evaporation layer and/or the skin attachment layer may be replaceable.

In a second aspect of the invention, an absorbent layer, preferably an evaporative layer, is provided for attachment to a medical device having a removable evaporative layer.

In a third aspect of the invention, a skin attachment layer is provided for attachment to a medical device having a removable skin attachment layer. The skin attachment layer may comprise at least one microneedle.

In a fourth aspect of the invention, there is provided a method of analyzing a body fluid, the method comprising the steps of: attaching the device to the skin of a user; collecting bodily fluid from a user using at least one microneedle; analyzing the body fluid using an analysis unit; allowing at least a portion of the fluid to be absorbed by the evaporation layer; and allowing at least a portion of the fluid to evaporate from the evaporation layer.

Drawings

The accompanying drawings, which are incorporated in and form a part of the specification, schematically illustrate preferred embodiments of the present invention and, together with a description, serve to explain the principles of the invention.

Fig. 1 is a schematic cross-sectional side view of a medical device attached to the skin of a user.

Fig. 2 is a schematic cross-sectional side view of a hollow microneedle array.

Fig. 3 is a schematic diagram of various electronic units in the medical device.

Fig. 4 is a schematic cross-sectional side view of a medical device.

Fig. 5 is a schematic cross-sectional side view of a medical device.

Fig. 6 is a schematic perspective view of a medical device.

Fig. 7 is a schematic cross-sectional side view of the medical device of fig. 6.

Fig. 8 is a schematic cross-sectional side view of a medical device including an elastomer.

Fig. 9 to 12, 13a and 14 are schematic side views of a medical device.

Fig. 13b is a schematic cross-sectional side view of a detachable evaporation layer.

Figure 13c is a schematic cross-sectional side view of the reusable part.

Fig. 13d is a schematic cross-sectional side view of a releasable attachment layer.

Fig. 14 shows the medical device attached to the skin of a patient.

Detailed Description

Referring to fig. 1, a medical device 1 is used for attachment to skin 2 and analysis of bodily fluids. For example, the body fluid may be blood or interstitial fluid, with interstitial fluid being preferred. Suitable locations for the attachment device 1 may include an arm, such as an upper arm or thigh.

The medical device 1 preferably has the shape of a patch or a flat housing. The device has at least one flat surface, which is an attachment surface 3 for attaching the device to the skin 2 of a user. At least one microneedle 4 protrudes from the attachment surface 3. The device 1 is intended to be attached to the skin 2 such that at least one microneedle 4 is inserted into the body of the user. Thereby, the microneedles 4 penetrate the outer surface of the skin 2.

At least one hollow microneedle 4 is used to extract body fluid from the body. Preferably, there is an array 5 comprising a plurality of microneedles 4. When the array 5 is present, the microneedles 4 are preferably arranged substantially in the same direction. The microneedles 4 may be oriented at about 90 ° (perpendicular) with respect to the skin attachment surface 3, or may be slightly inclined with respect to the skin attachment surface 3. Referring to fig. 2, which shows an array 5 having a plurality of microneedles 4, at least one microneedle 4 is hollow and has at least one opening 24 near or at a tip 25 for receiving a bodily fluid. The length of the microneedles 4 is preferably as short as possible to minimize discomfort (e.g. pain) to the user, but should still be long enough to sample the body fluid of interest in a reliable manner. Blood sampling may require longer microneedles 4 and therefore may be more desirable for sampling interstitial fluid. The microneedles may be 50 to 3000 μm in length, preferably 100 to 2000 μm, more preferably 200 to 1500 μm. The hollow microneedles may have an inner diameter in the range of 15 μm to 300 μm, for example. The microneedles 4 are preferably made of metal, silicon or a polymer material or ceramic. Useful materials include platinum, titanium, iron, gold, nickel, copper, gold, or alloys of these metals. Stainless steel is also a useful material. US9033898 and references therein, and Wentrelli (Ventrelli) et al (Adv Helthcar Mater, 2015, DOI: 10.1002/adhm.201500450) provide information about suitable microneedles, arrays, and their production.

The array 5 may have any suitable number of microneedles 4. For example, 1, 2, 3 or more, such as 10 or more, such as 100 or more, such as up to 500 microneedles 4. When a plurality of microneedles 4 are present, they may be arranged along a straight line or as a matrix, for example, in a square or circular arrangement.

Due to the elasticity of the skin 2, it may be necessary to insert at least the microneedle 4 or the microneedles 4 into the skin using an applicator. An adhesion speed of 1m/s to 20m/s may be useful. The applicator may generate 4m/s²To 100000m/s²Of the acceleration of (c).

Returning to fig. 1, a microneedle 4 or a plurality of microneedles 4 are connected to the flow channel 6 so that fluid collected in the microneedle 4 can flow into the flow channel 6. The microneedle array 5 or all microneedles 4 of the device 1 may be connected to the same flow channel 6 by a branching system 7.

The bodily fluid flows from the body of the user into the opening 24 of the at least one microneedle 4 and from the microneedle 4 into the flow channel 6. The fluid then passes or passes the analysis unit 8, where at least a part of the fluid is analyzed. The flow channel 6 continues on the other side of the analytical unit 8. The fluid then flows out into a storage layer, preferably an evaporation layer 9, where the water component of the fluid is absorbed and then evaporated. Alternatively, the absorption layer may be a storage layer (see below). The analysis unit 8 may be incorporated into a portion of the flow channel 6. The analytical unit 8 may be, for example, an electrode arranged in the flow channel 6.

Flow through the device 1 may be achieved at least in part by evaporation from an absorbent layer (which may be an evaporation layer 9), or absorption of fluid by an absorbent layer (which may be an evaporation layer 9), or by a pump 10 (fig. 10), or a combination thereof. The flow may be caused by capillary action and/or wicking action and/or evaporation of the absorbent layer (which may be the evaporation layer 9) without the aid of the pump 10. Thus, in some embodiments, flow through the flow channels in the device may occur without the aid of the pump 10. In some embodiments, the pump 10 is used to start the flow of fluid through the device 1 and then stop operation.

The flow channels 6 may be in a pre-wetted state such that they are delivered into the channels 6 together with some fluid (e.g. water) to start evaporation and flow through the flow channels 6. However, capillary action may be sufficient to provide the initial flow rate. Capillary action is best achieved by a relatively thin flow channel.

The pump 10 may be such that it is only used to induce flow from the microneedles 4 to the absorbent layer so that once the flow channel 6 is filled, the absorbent layer can drive the flow. This may be useful if the capillary flow is not sufficient to initiate flow. The pump 10 may then preferably be a disposable pump, e.g. a prepackaged vacuum chamber, or a chamber that changes its shape by means of e.g. electromagnetic forces or electric currents. The task of the disposable pump 10 is to fill the flow chamber 6 from the microneedles 4 to the evaporation layer 9 with body fluid. The pump 10 may be such that it stops once flow through the device 1 is established. The disposable pump can be activated by attaching the device 1 to the skin 2. For example, the disposable pump may be activated by body heat. Alternatively, the attachment surface 3 may have a protrusion or button that is displaced when the user attaches the device to the skin, and the button may cause suction in the flow channel 6. As a third option, the pumping action may be caused by the user pressing a button.

The flow channel 6 is preferably a microfluidic channel. The flow channels 6 are typically less than 1mm in diameter, more preferably less than 500 microns in diameter, and in some embodiments less than 50 microns, and in some embodiments less than 1 micron in diameter. The flow channel 6 may be formed by a part of the housing 18 or the inner housing 28, or may be formed by a separate pipe. The pipe material of the flow channel 6 may for example be a polymer material, but for example also metal may be used.

The flow rate of the device 1 may be selected so as to obtain a reliable analysis, typically measurement of the analyte concentration, while keeping the device 1, in particular the microneedles 4, as small as possible. Any useful flow and analysis plan may be used. The flow rate through the device 1 may be between 1 nl/hour and 300. mu.l/hour, with 100nl to 30. mu.l/hour being preferred. It may be necessary to use pump 10 to obtain higher flow rates. The flow may be more or less constant or may vary over time. For example, the flow may increase at certain points in time, or may stop or nearly stop at other points in time. The flow in the flow passage 6 can be controlled using a pump 10 or a valve. The valves and pump 10 may be controlled by a processor 11.

The optional pump 10 may be any type of mechanism that generates suction or pressure. In one embodiment, the pump 10 is driven by electricity. The pump 10 may be, for example, a piezoelectric or electromechanical device. Alternatively, the pump 10 may be a prepackaged vacuum chamber, or another device that creates a vacuum, for example by means of memory foam, or a chamber that changes its shape over time to create suction or pressure. The pump 10 may be placed between the microneedle 4 and the analysis unit 8, or between the analysis unit 8 and the evaporation layer 9.

The analysis unit 8 is capable of detecting at least one property of the body fluid. The property may be the presence or concentration of an analyte. The analysis unit 8 may analyze any useful analyte. Examples of analytes include: glucose, pH, electrolytes, liver enzyme values, biomarkers, c-reactive proteins, immunoglobulins, drugs or their breakdown products, hormones or other signaling molecules, peptides or peptide fragments, toxins, metabolites, pathogenic agents such as bacterial or viral toxins or proteins, and lipids such as cholesterol. The biomarker may be an endogenous protein or a pathogen protein, such as a viral, bacterial or parasitic protein.

Any useful chemistry or method can be used to analyze the analyte. For example, electrical potentials, spectroscopy, fluorescence, immunoassays, light scattering, surface plasmon resonance, binding of specific reagents (e.g., antibodies) or enzymatic activity, or combinations thereof, may be used, as long as they can be miniaturized to the extent suitable for assembly into the device 1, particularly into the body 26 of the device 1 (see below).

Glucose is the preferred analyte. Thus, in a preferred embodiment, the device 1 is adapted to analyze the glucose level in interstitial fluid or blood of the user. Methods of detecting glucose levels are well known. Continuous measurement of glucose levels is suitably measured by conventional glucose oxidase chemistry using electrodes. Typically, three electrodes are used: a working electrode, a counter electrode and a reference electrode. Typically, glucose oxidase is used to catalyze H on the working electrode₂O₂Is generated. The glucose oxidase may for example be entrapped in a layer on the electrode. In order for this reaction to occur at the working electrode, an excess of O is required₂And a mediator compound may be used from H₂O₂Free electrons are generated to reduce the need for O2. Useful mediators include ferrocene derivatives, ferricyanides, conductive organic salts (especially tetrathiafulvalene-tetracyanoquinodimethane, TTF-TCNQ), phenothiazines and phenoxazine compounds or quinone compounds. Alternatively, glucose hydrogenase may be used as the enzyme. Venturi et al (Adv Helthcar Mater, 2015, DOI: 10.1002/adhm.201500450) provide information about useful glucose sensors.

Analyzing the glucose level of a user, in particular a diabetic patient, by analyzing interstitial fluid is a preferred embodiment. The glucose concentration in interstitial fluid is closely related to the glucose concentration in blood, but with a little time lag.

Other types of analytes that may be measured with electrodes include glutamate, ethanol, choline, cortisol, or lactate. For example, an electrode of the type sold by Pinnacle Technology, kansas, usa may be used. Preferably, the analysis unit 8 comprises at least one electrode 8 for measuring the presence or concentration of an analyte.

Referring to fig. 3, the apparatus 1 preferably comprises a processor 11 for collecting signals from the analysis unit 8, a memory 12 for storing measured values and software, and a wireless communication unit 13. The wireless communication unit 13 is preferably capable of communicating information to a second device 36, such as a smart phone or other type of wireless device or other type of device. Preferably, the sample data is transmitted with the time points for analysis or sampling. The data transmission may occur automatically when the second device 36 is within range of the medical instrument 1. The wireless communication may be of the Near Field Communication (NFC) type, for example bluetooth.

The apparatus 1 preferably includes a communication interface 14 for allowing communication between various electronic devices. There may be a power source, such as a battery and wires, for powering one or more of the analysis unit 8, the pump 10, the processor 11, the memory 12, the wireless communication unit 13 and the communication interface 14, and the sensors 23 (e.g., flow sensors or pressure sensors). The battery may be charged using an induction coil or port, or may be disposable. As an alternative to batteries, the device may have a self-powered biofuel cell (BFC). The analysis unit 8, the pump 10, the processor 11, the memory 12, the wireless communication unit 13, the communication interface 14, the battery and the sensor 23 are all referred to herein as an "electronic unit" 29. The device 1 may comprise other electronic units such as, but not limited to: sensors, alarms, lighting units, charging coils, valves, etc. These are also referred to as "electronic units" 29. The device 1 may have at least one electronic unit 29, in particular an electronic unit 29 which generates some heat as a by-product during its operation. For example, the wireless communication unit 13 generates at least some heat during transmission, and the processor 11 generates at least some heat while in operation.

The processor 11 and the software stored in the memory 12 control or receive data from various electronic units 29 of the device 1. The processor 11 and software may control the flow of the fluid tank apparatus 1 by controlling the pump 10 or valves. The sampling or analysis may be performed at any suitable interval and may be controlled by the processor 11. The sampling or analysis may be performed at least every predetermined timer interval, such as at least every 24 hours, more preferably at least every 12 hours, at least every 6 hours, at least every 3 hours, at least every 2 hours, at least every 60 minutes, at least every 30 minutes, at least every 15 minutes, at least every 10 minutes, at least every 5 minutes, at least every minute, at least every 10 seconds or at least every second. The pump 10 and valves may be operated with a sampling frequency. The data from the analysis unit 8 may be stored in the memory 12 together with the relevant point in time, e.g. the time and date of sampling or analysis. When the analysis is performed in a fluid flowing more or less continuously through the sensor (e.g. an electrode), the point in time of the analysis may be more relevant. In some embodiments, the fluid may be isolated prior to analysis, and in those cases the point in time of sampling may be more relevant.

The transfer of data to the second device 36 may be accomplished automatically on a predetermined schedule, which may be at least once per day, or at the convenience of the user. The user may initiate the data transfer, for example, by using the second device 36 to trigger the data transfer. The processor 11 may control the sampling, analysis and transmission of data to the second device 36 using the wireless communication unit 13. For example, device 1 and second device 36 may perform a handshake before transmitting data to second device 36. The second device 36 may be capable of storing data. The second device 36 is also capable of displaying data on the display. The second device 36 is also capable of transmitting data to the cloud solution for storage, analysis, and future reference.

The processor 11 and software may be configured to perform one or more of the following operations: monitoring the flow rate of fluid through the device 1, controlling the flow rate, controlling the pump 10 and/or valves, monitoring the proper functioning of the device 1, alerting when a malfunction occurs or replacement is required, checking the battery status, alerting when the flow rate is low, starting and stopping the device, resetting the device, wirelessly communicating with the second device 36, data analysis, data storage and transmission, data encryption, storing the ID of the device 1 and the second device 36.

Preferably, the device 1 is suitable for use for days or weeks, such as at least 3 days, more preferably at least 5 days, more preferably at least 10 days, most preferably at least 20 days. The device 1 is thus able to withdraw body fluid and analyze it over such a period of time.

Evaporation layer

The device has an absorbing layer. The absorption layer may be the evaporation layer 9 or the storage layer. The fluid handling capacity of the storage layer is based entirely or almost entirely on the absorption of fluid, while evaporation is negligible. All embodiments of the invention with an evaporation layer can also be used with a storage layer instead of the evaporation layer 9, as long as possible. An advantage of using a storage layer is that the absorbent material can be encapsulated, thereby enabling the user to use the device 1 in water, for example when swimming. Embodiments having an elastomer layer 27 are particularly useful for this, see fig. 8 (see below). However, in a preferred embodiment, the device has an evaporation layer 9 and the fluid treatment is at least partly based on evaporation. Thus, the evaporation layer 9 may assist in the evaporation of the fluid.

The fluid handling capacity of the apparatus 1 may be such that the fluid handled by the apparatus 1 is at least as fast as the flow rate in the apparatus.

Returning to fig. 1, the flow channels 6 distribute the fluid through the openings 37 into the evaporation layer 9. The flow channel 6 may branch into two or more branches 22 (shown in fig. 9 and 10) discharging into the evaporation layer 9 through the opening 37. Thus, the flow passage may have a plurality of openings 37. The purpose of the branches 22 is to diffuse the fluid in the evaporation layer 9. The evaporation layer 9 is adapted to receive fluid from the flow channel 6. The fluid is preferably water-based, such as interstitial fluid or blood. The purpose of the evaporation layer 9 is at least one of: a) the fluid collected by the microneedles 4 is processed by absorbing the fluid and then evaporating the fluid (wherein not necessarily all of the fluid evaporates), b) the flow through the device 1 is enhanced or caused by absorbing and by evaporating the fluid. Preferably, a) and b) are effected simultaneously.

The evaporation layer 9 is capable of absorbing and/or allowing the fluid to evaporate. Suitable evaporation layers 9 have a high fluid handling capacity. As used herein, "fluid handling capability"Refers to the combined ability to draw in (absorb) moisture and evaporate it into the environment (ambient air). For a layer of uniform thickness, the fluid handling capacity of the evaporation layer may be at least about 1g/m²24h, more preferably at least 10g/m²24h, more preferably at least 500g/m²24h, more preferably at least 1000g/m²Per 24 hours, more preferably 2500g/m²24 hours or at least about 3500g/m²And/24 hours.

The fluid handling capacity of the evaporation layer 9 may be based mainly on absorption and retention (storage) of the fluid, where evaporation is less important, or may be based mainly on evaporation, where a large part of the fluid is evaporated. Over time, in the initial stage of using the evaporation layer 9, storage may be a more important component, and evaporation may be a more important component as the evaporation layer reaches saturation. At steady state, all fluid handling capacity may be provided by evaporation. In an embodiment, during use, at least 50%, more preferably 60%, even more preferably 70%, even more preferably 80%, even more preferably 90%, even more preferably 95%, and most preferably at least 99% of the total fluid handling capacity of the evaporation layer is provided by evaporation.

Moisture Vapor Transmission Rate (MVTR) is a measure of the passage of water vapor through a substance. In one embodiment, the evaporation layer 9 has a high MVTR. The MVTR of device 1 may cause the fluid to evaporate at the same rate or faster than the flow rate of the fluid in device 1, such that all of the fluid reaching the evaporation layer 9 evaporates over time. When the evaporation layer 9 has a uniform thickness, it has an MVTR of at least 1g/m²Per 24 hours, more preferably 300g/m²24 hours, more preferably at least 500g/m²24 hours, more preferably at least 1000g/m²24 hours, most preferably at least 1200g/m²And/24 hours. A high MVTR is useful because it prevents the growth of antimicrobial agents and prevents the formation of moisture, thereby providing more comfort to the user. Methods for determining fluid handling and MVTR are described in WO 2013071007.

The evaporation layer 9 may be at least partially exposed to the surrounding air, which facilitates evaporation.

The evaporation layer 9 may comprise a material having a large surface area, such as a fluff layer, a foam layer, a porous layer or a sponge layer.

The evaporation layer 9 may comprise cellulose fibres, for example cellulose fluff (fluff pulp). Examples of useful materials include BASFTexsusAnd the like. Examples of absorbent materials are also provided in WO9620667 and WO 200115649.

The evaporation layer 9 may comprise or be formed from a hydrogel-forming absorbent polymer. Superabsorbent polymers include crosslinked acrylate polymers, crosslinked products of vinyl alcohol-acrylate copolymers, crosslinked products of polyvinyl alcohol grafted with maleic anhydride and carboxymethyl cellulose. BASF superabsorbent polymer comprisingAndbrands of polyacrylates are all useful.

The evaporation layer 9 may comprise cellulose fibres and a hydrogel-forming absorbent polymer.

When the absorption layer is the storage layer, it may comprise or consist of the same type of material as the evaporation layer. In particular, a hydrogel-forming absorbent of a forming polymer may be used for the storage layer.

The shape of the evaporation layer 9 may preferably be selected to have a large surface area. For example, it may have a more or less flat structure. Preferably, the thickness of the evaporation layer 9 is smaller than the width and length of the evaporation layer 9. The maximum thickness of the evaporation layer 9 is preferably at most 50%, more preferably at most 30%, of the maximum width of the device 1. When the device 1 is disc-shaped (fig. 6 and 7), the width is the diameter of the device 1.

The device may have an outer layer 39 which may be a breathable outer layer 39, most preferably a thin breathable layer outside the evaporation layer 9 (fig. 6-7). The outer layer 39 may be used to prevent water splashing, contamination or mechanical wear. The outer layer 39 may preferably comprise a nonwoven material or a film material. The material may be water vapour permeable. The outer layer 39 may, for example, have small holes or pores to increase breathability. The outer layer 39 may for example comprise or consist of polyurethane, elastic polyester or polyvinyl chloride. The outer layer may be of the Gore-Tex type, i.e. a material that is water-impermeable but still breathable.

Referring to fig. 4, the device 1 may preferably comprise an adhesive skin attachment layer 15 comprising the attachment surface 3. The adhesive attachment layer 15 comprises an adhesive compound or composition that adheres the device 1 to the outer surface of the skin 2 even on vertical body surfaces and during movement. The adhesive of adhesive attachment layer 15 may be an acrylate, including methacrylates and epoxy diacrylates. The adhesive may be a pressure sensitive adhesive. HenkelIs a useful adhesive. The adhesive attachment layer 15 may also include an elastomeric compound. The adhesive attachment layer may also be contained in a separate housing that is separable from the rest of the components of the device 1.

The adhesive attachment layer 15 may have a release liner 16 on the skin contacting side. The release liner 16 is removed prior to applying the device 1 to the skin 2 of a user.

Referring to fig. 1, 4 and 5-13 and 15, the medical device 1 may have any suitable shape. The medical device preferably has a body 26 comprising an attachment surface 3, wherein at least one microneedle 4 protrudes from the body 26. The body comprises the evaporation layer 9, the attachment surface 3, the main part of the flow channel 6, the analysis unit 8, the attachment layer 15 and any electronics unit 29. The body 26 may also comprise the base of the microneedles 4 such that the microneedles 4 protrude from the base integrated in the body 26. Preferably, the device 1 comprises a body 26 and at least one microneedle 4.

Preferably, the body 26 has a circular shape, for example a disc shape or a patch shape. The patch may be a soft patch. Preferably, the analysis unit 8 is comprised in the body 26 of the medical instrument 1. For example, inside the housing 18 or embedded in an elastomer 27 as described below, as described below. Therefore, it is preferable that no part of the analysis unit 8, such as the electrode, is inside the microneedle 4.

The analysis unit 8 and other components, such as other electronic components 29, may be disposed in the reusable part 21 (fig. 5, 7, 9 and 13) between the evaporation layer 9 and the adhesive attachment layer 15.

As shown in fig. 5, 6, 7, the device 1 may comprise an outer housing 18, wherein the evaporation layer 9 is placed on top of the outer housing 18 or in an upper compartment of the housing 18. Housing 18 may be made of a rigid polymeric material such as ABS, PET, PETG, or polycarbonate. The evaporation layer 9 is located on top of the housing 18 or in an opening in the housing 18 and may be held in place by a flange 19 (fig. 7).

The device 1 may comprise an elastomeric (rubber-like) material. The body 26 of the device may then be a soft patch. For example, the flow channel 6 and the base of the array 5 of microneedles 4, and at least one electronic unit 29, preferably the analysis unit 8, or all electronic units 29, may be contained in the elastomer layer 27. Referring to fig. 8, the elastomeric layer 27 may comprise or surround the vaporization layer 9, particularly the vaporization layer 9 that absorbs a substantial amount of fluid (e.g., hydrogel-forming polymer). This embodiment may be particularly useful when a storage layer is used instead of the evaporation layer 9. Preferably, the elastomer layer 27 is impermeable to water in the liquid phase, so that the storage or evaporation layer 9 is not wetted when the user swims or showers. In the embodiment shown in fig. 8, a hydrogel-forming compound is preferably used for the storage layer. The flow channel 6 and the analysis unit 8 can be accommodated in an inner housing 28, which inner housing 28 is embedded in the elastomer layer 27 and the evaporation layer 9. The inner housing 28 may also include other electronics units 29. The inner housing 28 may also include the base of the array 5. The conduits for the flow channel 6 and the inner housing 28 may be moulded in one piece of polymer material.

The elastomeric layer 27 may be breathable to allow water vapor to pass through. For example, the elastomer layer 27 may have pores. However, the fluid treatment may be based almost entirely on absorption in the evaporation layer 9 within the elastomer layer 27. The elastomer layer may thus have a low MVTR (low breathability) to protect the layer 9 from moisture from the outside.

Examples of useful elastomers include, but are not limited to, natural rubber, polyisoprene, styrene butadiene rubber, neoprene, polybutadiene, nitrile rubber, butyl rubber, ethylene propylene diene monomer, chlorosulfonated polyethylene, polysulfide rubber, Polyurethane (PU), EVA film, copolyester, and silicone.

Enhancement of evaporation

The evaporation of the fluid from the evaporation layer 9 may be enhanced by body heat from the user. The user can conduct or radiate body heat into the evaporation layer 9 through the attachment layer 15. When the thickness of the device 1 is thin, it is easy to heat the evaporation layer 9 by the body of the user, thereby bringing the evaporation layer 9 close to the body. The maximum thickness of the device 1 (measured from the attachment surface 3 to the top of the evaporation layer 9 or outer layer 39) is preferably less than 20mm, even more preferably less than 10mm, most preferably less than 5 mm.

The evaporation of the fluid from the evaporation layer 9 may also be enhanced by heat from the at least one electronic unit 29. The at least one electronic unit 29 may be arranged such that it is at least partially arranged in contact with the evaporation layer 9 (fig. 9). The electronics unit 29 may for example be selected from the group consisting of the analysis unit 8, the pump 10, the processor 11, the memory 12, the wireless communication unit 13, the communication interface 14, the sensor 23 and the battery.

The device 1 may comprise a heat conducting element 17. The heat conducting element 17 assists in the conduction and distribution of heat from the user's body and from any electronics unit 29 of the device 1 to the evaporation layer 9. The heat conducting element 17 may be, for example, a heat conducting layer, such as a metal film or foil as shown in fig. 10.

The heat conducting element 17 may be arranged between the adhesion layer 15 and the evaporation layer 9. At least a portion of the heat conducting element 17 is preferably in contact with the evaporation layer 9. The heat conducting element 17 may be arranged above the electronics unit 29 but below the evaporation layer 9 as shown in fig. 10, in order to transfer heat from the electronics unit 29 to the evaporation layer 9, thereby enhancing the evaporation. Thus, the heat conducting element 17 may be arranged between the evaporation layer 9 and one element selected from the group consisting of the analysis unit 8, the pump 10, the processor 11, the memory 12, the wireless communication unit 13, the communication interface 14, the sensor 23 and the battery. The heat conducting element 17 may be a layer substantially parallel to the skin attachment surface 3 as shown in fig. 10. However, the heat conducting element 17 may also be arranged as a vertical metal stud or a metal film or sheet, which conducts heat from the user's body to the evaporation layer (fig. 11). The heat conducting element 17 then preferably extends from close to the attachment surface towards the evaporation layer 9. A portion of the heat conducting element 17 may even be in contact with the outer surface of the skin 2 of the user when the device 1 is attached to the skin 2. For example, the studs in the figures may be in contact with the surface of the skin 2. In general, the heat conducting element 17 may be arranged to conduct heat in a direction perpendicular to the attachment surface 3 and towards the evaporation layer 9.

The heat conducting element 17 or the electronic unit 29 may comprise heat conducting surface area increasing elements, such as heat conducting heat dissipating fins 20 or similar devices, which increase the surface area for conducting heat to the evaporation layer 9. The heat radiating fins 20 are preferably made of a material having high thermal conductivity, such as metal. A portion of the surface area increasing means, such as heat dissipating fins 20, may be embedded in the evaporation layer 9. The electronic unit 29 may have metallic heat sink fins 20 attached to its outer surface, with the metallic heat sink fins 20 being immediately adjacent to or embedded in the evaporation layer 9 (fig. 9). For example, the processor 11, the analysis unit 8 or the wireless communication unit 13 may be arranged next to the evaporation layer 9 and have heat dissipation fins 20 embedded in the evaporation layer 9. Instead of the heat radiating fins 20, a metal wire, a metal mesh, or the like may be used. As another example, the heat conducting element 17 may be a corrugated metal foil, one side of which is embedded in the evaporation layer 9 (fig. 12).

Fig. 9 and 10 also show the communication interface 14 of the device 1.

Antibacterial agent

The device 1, in particular the evaporation layer 9, may comprise an antibacterial, in particular antibacterial, antifungal or antiviral agent. Other parts that may comprise the antimicrobial agent are the at least one microneedle 4, the inner surface of the flow channel 6 and the analysis unit 8.

In one or more embodiments, the antibiotic agent is selected from the group consisting of beta-lactam antibiotics, aminoglycosides, ansa-type antibiotics, anthraquinones, antibiotic azoles, antibiotic glycopeptides, macrolides, antibiotic nucleosides, antibiotic peptides, antibiotic polyenes, alcohols, antibiotic polyethers, quinolones, antibiotic steroids, sulfonamides, tetracyclines, dicarboxylic acids, antibiotic metals, oxidizing agents, free radical and/or reactive oxygen species, cationic antimicrobials, quaternary ammonium compounds, biguanides, triguanidines, biguanides and analogs and polymers thereof, and naturally occurring antibiotic compounds.

Examples of particularly useful antibacterial agents may be p-chloro-m-xylenol; chlorhexidine and its salts, such as chlorhexidine acetate and chlorhexidine gluconate; iodine; iodophors; poly-N-vinylpyrrolidone-iodophor; silver oxide, silver and its salts, alginic acid, sodium fucosylate, retamo-morelin, mupirocin, oxytetracycline, polymyxin B, kanamycin, bacitracin zinc, neomycin, lactic acid, citric acid, and acetic acid.

Examples of antifungal agents which may be used in the present invention and which are topically applied are amoxprofen, clotrimazole, miconazole, ketoconazole, ciclopirox or terbinafine.

The antimicrobial agent is preferably solid at room temperature, preferably at a temperature of up to 35 ℃. This temperature may be required in order to maximize evaporation of body fluid from the evaporation layer 9.

Components of the device 1, such as the at least one microneedle 4, or the inner surface of the flow channel 6, or the inner surface of the evaporation layer 9, may also include a surface treatment or coating that inhibits microbial growth. Examples of such coatings or surface treatments are: devices for inhibiting bacterial attachment, agents for disrupting the cell membrane of microorganisms, such as surfactants or transmembrane proteins, and the use of silver ions.

Replaceable component

In certain embodiments referring to fig. 13 a-13 d (which may be combined with other embodiments), at least one of the vaporization layer 9 and the adhesive attachment layer 15 (including the microneedles 4) of the medical device 1 may be replaced. Thus, the evaporation layer 9 may have a lower surface 30 removably attached to an upper surface 31 of the rest of the device 1. The attachment layer 15, including the attachment surface 3, may have an upper surface 32 that is removably attached to a lower surface 33 of the remainder of the medical device 1, such as the housing 18 or the elastomeric layer 27.

In a preferred embodiment, the evaporation layer 9 and the attachment surface 3 can be replaced, while the reusable part 21 comprising at least one electronics unit 29, in particular the analysis unit 8, is reusable. Preferably, reusable component 21 includes other electronics unit 29, such as pump 10, processor 11, memory 12, wireless communication unit 13, which may be expensive and therefore may be reused.

In one embodiment, the battery is provided in one of the replacement parts 9 or 15. Thus, when the evaporation layer 9 or the adhesion layer 15 is replaced, the battery is replaced. The power supply cable between the battery and the electronic unit 19 may then have a physical connector in much the same way as the channel 6 (see below with reference to fig. 13 a).

The evaporation layer 9 (fig. 13b) or the attachment layer 15 (fig. 13d) or both may thus be reversibly attached to the rest of the device 1, e.g. the reusable part 21 (fig. 13b), e.g. by means of an adhesive. The adhesive is preferably of a type that allows attachment and detachment without damaging reusable component 21. The connection can also be achieved by means of, for example, micro velcro or similar means.

Reusable component 21 may have any suitable design. For example, the reusable component 21 may include the outer housing 18. When the device has the embodiment of fig. 8, the reusable component can include an inner housing 28.

The releasable attachment layer 15 of fig. 13a and 13d may comprise a housing (separate from the housing 18) or may comprise a body of elastic material.

Preferably, the replaceable attachment layer 15 comprises microneedles 4, such as an array 5 of microneedles 4. The microneedles 4 or the lower portion of the flow channel 6a may be connected to the rest of the flow channel 6b by connectors 24a and 24b (fig. 13a, 13c, 13 d). Preferably, the connection between connectors 24a and 24b is leak proof, such as by means of a gasket or a press fit, or both. The connectors 24a and 24b may be snap-locked, for example, the connectors 24a, 24b may snap together.

Flow channel 6 can terminate at upper surface 31 of reusable component 21 such that when the evaporative layer is attached to reusable component 21, flow channel 6 spills into evaporative layer 9. Alternatively, the replaceable evaporation layer may have a continuation of the flow channel (fig. 13b) which is connected to the flow channel 6b by a connector similar to the connectors 24a and 24 b. This is particularly useful when the flow channel has branches in the evaporation layer 9 (fig. 9 and 10).

The replacement of the skin attachment layer or the evaporation layer may be triggered by different events, for example at certain points in time. For example, the evaporation layer or the skin attachment layer may be replaced within a predetermined time period, which may be, for example, 7 days or 14 days. Preferably, the replacement may be performed by the user himself. The device 1 may have an alarm or chemical color indicator that alerts the user to the replacement. For example, the processor 11 may trigger an audible alarm after a predetermined point in time. The evaporation layer 9 may be provided with a chemical color change indicator that changes color after being wetted for a certain time.

Further considerations

As shown in fig. 14, the device 1 may have an upper end 34 and a lower end 35, the flow channel 6 discharges into the evaporation layer 9, and the position where the flow channel 6 discharges into the evaporation layer 9 is closer to the upper end 34 than the lower end 35. Such an arrangement will improve the distribution of liquid in the evaporation layer 9 when the device 1 is placed on a part of the skin 2, typically a vertical or almost vertical surface, for example the side of an upper arm, at least when the user is not lying down, as gravity will tend to cause the fluid to flow from the opening 37 of the flow channel 6 down into the evaporation layer 9. The flow path may have branches 22 providing a plurality of openings 37.

In general, the body 26 of the device 1 may have any suitable shape. Fig. 15 shows a medical device 1 in the shape of a patch, which medical device 1 is attached to the skin of an arm of a patient. The device 1 of fig. 15 has a body 26 in the shape of a patch in the shape of a square with rounded edges. The shape of the patch may be circular, oval or have any suitable shape. Preferably, the body 26 is as flat as possible. As shown in fig. 15 and other figures, the edges of the main body 26 are preferably rounded to avoid catching on clothing and the like.

The shape and dimensions of the device 1 and the attachment layer 15 should be chosen such that the device 1 can be worn and carried by a user. Preferably, the user should be able to maintain his or her normal lifestyle, including working, performing exercise, etc., while wearing the device 1.

There is also provided a method of analyzing a body fluid, the method comprising the steps of: attaching the device 1 to the skin of a user; analyzing a body fluid from a user; allowing at least a portion of the fluid to be absorbed by the evaporation layer 9; and allowing at least a portion of the absorbed fluid to evaporate from the evaporation layer 9. The method may comprise the step of replacing the replaceable adhesion layer 15 or the replaceable evaporation layer 9.

The skilled person understands that the various embodiments of the invention may be combined whenever possible. Although the present invention has been described with reference to specific exemplary embodiments, the description is generally only intended to illustrate the inventive concept and should not be taken as limiting the scope of the invention. The invention is generally defined by the claims.