DE10335611A1 - Plaster for obtaining a skin liquid primarily for diagnostic purposes comprises means for vacuum generation, for collection and transfer of the liquid, and for insertion of test strips and/or sensors or their contact elements - Google Patents

Abstract

The plaster with an adhesive contact surface, for obtaining a skin liquid primarily for diagnostic purposes comprises means for vacuum generation, for collection and transfer of the liquid, and for insertion of chemical test strips and/or electrochemical sensors or their contact elements.

Description

The Invention relates to patches for obtaining skin fluid, especially for improving the efficiency and safety of dermalers and transdermal diagnoses.

When dermal or transdermal diagnostic systems can be such classify technical devices placed on or in the skin and with those from skin layers information about body texture can be achieved. This includes for example, information about the qualitative or quantitative content of endogenous or foreign body Substances, for example the blood content of electrolytes and glucose, of drugs, alcohol or drugs.

It it is known that the Obtaining blood as an analyte is the main source of diagnostic procedures is. For example, in the field of diabetes, this is a painful Procedure, as this, to add a drop of blood for glucose determination win, here only with a lancet one stitch into the dermis, which contains both blood capillaries and nociceptors got to. This drop of blood is then, as a rule, on a chemical Test tire given and this electronically evaluated thereafter. The process of obtaining blood is therefore not only painful, but also awkward and elaborate.

It it is known that, for example the glucose levels of the dermal interstitial fluid (ISF) in the thin upper Layers of the epidermis directly correlate with the glucose levels in the blood (Bantle JP, Thornas W, J. Lab. Clip Med. 130 (1997) 436-41) and that the ISF even with very small volumes comparable accuracy as in capillary blood (Service FJ, O'Brien PC, et al., Diabetes Care, 20 (1997); 1426-1429) allows. As a micro-invasive method with epidermal interstitial fluid as an analyte also anatomically in the area of largely nociceptor poor as well as vascular-free Epidermis is a determination here painless and blood free. The very thin In addition, upper epidermal layers require only very short invasive Distances.

Also is known to be also different substances, for example electrolytes, some antibiotics, qualitative, semi-quantitative or even quantitative skin fluid lying on the surface of the skin, especially the sweat, let determine. The difficulty is but that practice-oriented technical devices for the extraction, and possibly also for simultaneous evaluation of these skin fluids, do not exist.

Of the Transfer of substances in the skin basically follows the physical principles a passive diffusion. The molecules can be doing the skin either transcellular, i.e. through the cells, or intercellular, i. across the cells located between the cells interstitial spaces, penetrate. In a diffusion from the capillaries to the epidermal surface is the uppermost keratinous skin layer, the stratum corneum, the main barrier.

Of the Invention is the object of the efficiency and safety dermal and transdermal diagnoses.

These Task is solved by that for gaining of skin fluid as a multicomponent system composite patches are used these being from pressure lines for Devices for generating negative pressure, a plate-like and with microchannels provided with a device for collecting and conducting liquid, Devices for insertion or connection of electronic chemosensors or chemical test tire, as well as a skin-side attached adhesive surface are composed.

In Another embodiment of the invention are the practical Use to enhance and expand into this extra electrical, electronic, magnetic, optical, micromechanical, chemical or chemotechnical components, or combinations thereof, implemented.

In Another embodiment of the invention is to the practical Use to enhance and expand the collection device as platelike Platform formed, open into the one or more microchannels, wherein the mouths of the channels on the platform surface may be formed in different geometric patterns, wherein the channels with the skin surface or the epidermal skin layer, and wherein the platform at the same time a proportion of a measuring chamber for chemical Test tires or electronic chemosensors forms over which the liquid in contact with them, directly or indirectly analyzed and evaluated.

In another embodiment of the invention, in order to enhance and expand practical use, the printing apparatus is adapted to create a negative pressure on the skin area underlying the fluid collection, and either directly on the skin surface or below the surface of the skin Liquid in the channels of the liquid collection device is transported.

In Another embodiment of the invention are the practical Use to improve and expand the pressure lines with devices for Provided pressure equalization.

In Another embodiment of the invention to the practical Use to enhance and expand the patches as dermal or transdermal non-invasive or micro-invasive diagnostic systems for sweat or dermal interstitial fluid, especially for their analysis for glucose, lactate, electrolytes, adrenalin, creatinine, Alcohol, as well as those used by drugs and drugs.

In Another embodiment of the invention is to the practical Use to enhance and expand the patch as transdermal micro-invasive diagnostic system used, wherein the fluid collection via a plate-like collection device is provided with such microcannulas is the suitable to penetrate the uppermost epidermal skin layer.

In Another embodiment of the invention to the practical Use to improve and dilate the plasters as dermal or transdermal non-invasive or micro-invasive diagnostic systems are used, wherein the sensor devices used as planar electronic chemosensors are designed.

In Another embodiment of the invention to the practical Use to enhance and expand the patches as dermal or transdermal non-invasive or micro-invasive diagnostic systems are used, wherein in the electronic sensor devices at the same time pressure lines are integrated

In Another embodiment of the invention to the practical Use to improve and dilate the plasters as dermal or transdermal non-invasive or micro-invasive diagnostic systems are used, in which the electronic sensor devices can be inserted and removed in this reversible.

In Another embodiment of the invention to the practical Use to enhance and expand the patches as dermal or transdermal non-invasive or micro-invasive diagnostic systems used in which the analysis of the liquid by means of reversible in this retractable and removable chemical test tire takes place.

In Another embodiment of the invention to the practical Use to enhance and expand the patches as dermal or transdermal non-invasive or micro-invasive diagnostic systems are used, whereby chemical test strips are used in the connections for pressure lines are integrated.

In Another embodiment of the invention is to the practical To improve and expand the operation, production takes place in Parts or in whole technically in roll-to-roll procedures

In A further embodiment of the invention takes place to the practical Use to enhance and expand the production of the device for Insert or connection for electronic sensors or chemical test tires as a separate container made of chemically-synthetic polymers or natural material.

In A further embodiment of the invention takes place to the practical Improve and expand the production of the collection and guiding device for the liquid by mechanical pressing, punching or rolling, punching through Laser, thermally by melting, casting or foaming process, or a combination of such methods, and wherein the used Material a chemical-synthetic material, a metallic material, or a silicon-based material.

In A further embodiment of the invention takes place to the practical Improve and expand the production of the collection and guiding device in parts or in whole technically in roll-to-roll method

In a further embodiment of the invention take place to the practical Use to enhance and expand the pressure generation, data acquisition, Data storage, data evaluation and data display as well as energy supply using a common mobile device to which the electronic Sensors or the chemical test strips directly connected, or can be inserted into this for evaluation.

In Another embodiment of the invention is to the practical Improve use and expand, this also in the animal sector used.

Advantages of the invention result in particular from the fact that the patches enable a painless and blood-free liquid production of both superficial and dermal interstitial fluid, and at the same time serve as a technical platform for their analytical evaluation. This allows a noninvasive as well as micro-invasive diagnosis of endogenous substances, for example those of electrolytes and glucose, but also of pharmacologically active foreign substances, for example, of drugs, alcohol or drugs.

Especially in the field of glucose determination in diabetics is such a Measure advantageous because the current approach capillary Blood collection, which is achieved by invasive puncturing, usually the finger, done with a lancet, for These patients are painful and also awkward. For example a micro-invasive Method, i. such over the interstitial fluid the skin as an analyte, in the area of anatomical largely of Pain receptors (nociceptors) as well as blood vessels free Epidermis plays, this is therefore painless and blood free. Next to the Advantage of this considerable pain reduction or more completely Painless, so is the application security, through a reduced risk of infection, significantly higher than that of the currently invasive Method.

One Another advantage of the invention is that the patches for both new electronic Biosensors as well for conventional chemical test tires can be used. moreover becomes the technical execution The measurement itself greatly facilitates what is happening in children as well as older ones People of practical concern is. The measurements can also repeated as well as carried out mobile become what the independence for the Patients increased. Furthermore, there is the advantage of versatility. So can with the same patch, depending on the sensor or test strip used, different chemical parameters are measured.

One technical advantage is that the Plaster with usual Means of production in sufficient quantities Numbers economically, exactly standardized and manufactured reproducibly as well as application-related variable dimensions.

principal Technical examples of the invention are without reference to these examples technically restrict wanting to, explained below:

1 shows a schematic cross-section of the principal multi-component structure of a dermal vacuum plaster. Here, the flexible carrier plaster of polymer, in this technical example, of two layers, a lower part ( 1 ) and an upper part formed as a cover layer ( 2 ). In the upper part there is an opening ( 3 ) as a short pressure line, and in the lower part of a micro-channel perforated plate for liquid collection ( 4 ), the sampler, whose underside, in this case, micro-cannula-like bulges ( 5 ) Has. To the top pressure line ( 3 ) is an external, socket-like connection element ( 6 ) is docked to the pavement, which in turn is connected to a flexible 7 ) is connected to a printing device.

The two plaster layers also form by recesses a defined space ( 8th ), which serves laterally as a mechanical insertion device for an electronic sensor or a chemical test strip. The end part of the insertion device is dimensioned such that the measuring or reaction area of the sensor or of the test strip is positioned directly above the sampler. Therefore, this part also has the function of a measuring chamber, the bottom of the plate of the sampler ( 4 ). On the underside the plaster is provided with an adhesive layer ( 9 ), which fixes it to the skin while sealing the area around the sampler.

When generating suction via the docked pressure element ( 6 ), a negative pressure is generated in the space above the sampler, which acts on the upwardly open channels of the sampler and thus, in addition to the cohesive capillary force, also an active boost of the liquid contained in the microchannels generated. This places it on the surface of the sampler plate ( 4 ). When pressure is exerted also closed due to their elasticity, the upper and lower halves of the patch in the thin, slot-like insertion device. This takes place in the sense of a valve which closes like a sail in the manner of a sail, so that no pressure compensation takes place from this side. Alternatively, flat one-way valves can also be installed here. When pressure is released, these open again, due to the elastic elasticity of the paving material. When inserted, for example, a chemical test strip, then its reaction area is exactly opposite to that of the promoted on the platform of the sampler liquid and can react in direct contact with this.

In this technical example, epidermal interstitial fluid (ISF) can therefore be used as a microcannula. equipped microchannels ( 5 ), which in turn are submerged in the ISF of the epidermal skin layer, are taken up and sucked into the microcannulas by the negative pressure exerted via the pressure element, from which they then reach the sampler surface (FIG. 4 ) and then passes there for evaluation to the test field of an inserted test strip or sensor. Since the upper epidermal layers are very thin, they only require invasive distances of about 1-1.5 mm for microcannulas. Since this layer of skin is also largely free of blood vessels and terminal pain receptors, for this technical example, the painless and blood-free micro-invasive diagnosis of such substances is suitable, which come from the systemic circulation in the interstitial fluid epidermal layers of skin, and technically, for example with chemical test strips or electronic chemosensors, are detectable. These include, for example, glucose, lactate, electrolytes, adrenaline, creatinine, certain medicines or certain drugs.

2 shows the device of 1 in a schematic view as an explosion diagram, wherein here is a reversibly insertable, planar sensor ( 10 ), which is connected via a flexible line ( 11 ) is connected to an evaluation device.

3 shows in perspective a schematic of a technical example of a sampler, the collecting and guiding device for the skin fluid ( 4 ). In this case, the mouths of the microchannels ( 5 ), which are cannulated on the outermost side facing the skin. This technical training can be generated for example via a mechanical pressing or punching process. The mouths of the microchannels on the upper side are in this example also in a flat, trough-like recess ( 12 ), which also serves as the bottom of a measuring chamber for the sensors or test strips.

4 shows schematically in cross section a further embodiment of the multi-component plaster. The upper patch here is altogether as a sensor ( 10 ), which, in addition to its integrated electrochemical sensor element ( 13 ) at the same time an integrated pressure line ( 7 ) contains. Unlike in the examples of 1 - 3 is the sampler plate ( 4 ) in the lower patch part ( 1 ) but not on the skin side with microcannules but only sieve-like, with microchannels ending flush on both sides. The use of such kind of technical embodiment of the sampler is therefore only suitable to absorb superficial on the skin lying liquid, such as sweat. Next to the sampler plate ( 4 ) is located in the lower patch part ( 1 ) a short pressure line ( 3 ). On the underside the plaster is provided with an adhesive layer ( 9 ), which fixes it to the skin while sealing the area around the sampler. When flanging the top sensor ( 10 ) on the lower pavement ( 1 ) forms above the sampler ( 4 ) a closed chamber, wherein the pressure line from the pressure line of the patch ( 3 ) and the pressure line of the sensor part ( 7 ), and wherein the electrochemical sensor element ( 13 ) then directly above the sampler plate ( 4 ) contacted the liquid located on this, and via a flexible conduit ( 11 ) is connected to an evaluation device.

Claims (18)

Patch for deriving skin fluid, in particular for improving the efficiency and safety of dermal and transdermal diagnoses, characterized in that it is designed as a multi-component system with pressure lines for negative pressure generating devices, a plate-like and micro-channeled liquid collecting and conducting device for insertion or connection of electronic chemosensors or chemical test tires, as well as a skin-side attached adhesive surface are composed. Devices according to claim 1, characterized that in this extra electrical, electronic, magnetic, optical, micromechanical, chemical or chemotechnical components, or combinations thereof, are implemented. Devices according to the preceding claims, characterized characterized in that Collection device as a plate-like Platform is formed, open into the one or more microchannels, wherein the mouths of the channels on the platform surface may be formed in different geometric patterns, wherein the channels with the skin surface or the epidermal skin layer, and wherein the platform at the same time a proportion of a measuring chamber for chemical Test tires or electronic chemosensors forms over which the liquid in contact with them, directly or indirectly analyzed and evaluated. Devices according to the preceding claims, characterized characterized in that Printing device is designed so that it on the below for the liquid collection lying skin area generates a negative pressure, either directly on the skin surface lying or under the skin surface lying liquid into the channels the Flüssigkeitsammelvorrrichtung promoted becomes. Devices according to the preceding claims, characterized characterized in that Pressure lines are provided with devices for pressure equalization. Devices according to the preceding claims, characterized characterized in that Plasters as dermal or transdermal non-invasive or micro-invasive Diagnostic systems for Sweat or dermal interstitial fluid, especially for their analysis on glucose, lactate, electrolytes, adrenalin, creatinine, alcohol, as well as those of medicines and drugs. Devices according to the preceding claims, characterized in that the patches are used as a transdermal micro-invasive diagnostic system, the fluid collection via a plate-like collecting device is provided, which is equipped with such micro-cannulas, which are suitable to penetrate the uppermost epidermal skin layer. Devices according to the preceding claims, characterized characterized in that Plasters as dermal or transdermal non-invasive or micro-invasive Diagnosis systems are used, wherein the sensor devices used are designed as planar electronic chemosensors. Devices according to the preceding claims, characterized characterized in that Plasters as dermal or transdermal non-invasive or micro-invasive Diagnostic systems are used, wherein in the electronic sensor devices at the same time pressure lines are integrated Devices according to the preceding claims, characterized characterized in that Plasters as dermal or transdermal non-invasive or micro-invasive Diagnostic systems are used, in which the electronic sensor devices can be inserted and removed in this reversible. Devices according to the preceding claims, characterized characterized in that Plasters as dermal or transdermal non-invasive or micro-invasive Diagnostic systems are used, in which the analysis of the liquid by means of reversibly insertable and removable chemical Test tire is done. Devices according to the preceding claims, characterized characterized in that Plasters as dermal or transdermal non-invasive or micro-invasive Diagnostic systems are used, using chemical test strips be in the connections for pressure lines are integrated. Devices according to the preceding claims, characterized characterized in that Production in parts or in whole technically in roll-to-roll Procedure is done. Devices according to the preceding claims, characterized characterized in that Production of the device for insertion or connection for electronic Sensors or chemical test tires as a separate container chemical-synthetic polymers or a natural material. Devices according to the preceding claims, characterized characterized in that Production of the liquid collecting and guiding device by mechanical means Pressing, stamping or rolling, punching by laser, thermal through Melting, casting or foaming process, or a combination of such methods, and wherein the used material a chemical-synthetic material, a metallic Material, or a material based on silicon. Devices according to the preceding claims, characterized characterized in that Production of the collecting and guiding device for liquid in parts or in All technical in roll-to-roll procedure. Devices according to the preceding claims, characterized characterized in that pressure generation, Data acquisition, data storage, data evaluation and data display as well as energy supply by means of a common mobile device, to that the electronic sensors or the chemical test strips directly connected, or inserted into this for evaluation can be. Devices according to the preceding claims, characterized characterized in that also be used in the animal sector.