Drug delivery system

Abstract

To provide a drug delivery system enabling to dose drugs like insulin or in general fluids in a manner having an improved trade-off regarding usability, accuracy of the delivered fluid and cost efficiency.SOLUTION: A drug delivery system 10 comprises: a reservoir 16 having a meander shape or spiral shape, the reservoir comprising an inlet 16i and a filter; a capacitance measurement device 14 configured to determine a parameter of the reservoir; and a micropump 12 configured to deliver a fluid from the reservoir to an outlet.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] SUMMARY OF THE DISCLOSURE The present invention relates to a drug delivery system. [Background technology]

[0002] There are many medical applications that require small amounts of regular drugs or medications to be delivered to the body, e.g. People with diabetes who need insulin to keep their blood sugar at healthy levels Hormone therapy ·Pain treatment Treatment of Parkinson's disease Injection for premature babies Nuclear medicine (administration of nuclear markers) However, there are also new therapies such as the administration of monoclonal antibodies for the treatment of different cancer diseases, arthritis, rheumatism, multiple sclerosis, Alzheimer's, megrims, etc.

[0003] Most of these applications are subcutaneous drug delivery and some of them are intravenous infusions. There are several patents / patent applications mentioned in the context of drug delivery systems: these are EP 1 320 727 describing a fluid reservoir with measurement of fluid level by capacitance measurement, US 8,382,452 describing a safety valve, and WO 2011 / 107162 describing a bending transducer.

[0004] Below we consider the general prior art, for example in the context of diabetes treatment. There are several possibilities for administering insulin subcutaneously: 1. Syringe or pen: Patient must break the skin several times a day 2. Tethered Pump: A portable pump that has been on the market since the early 90's. The pump sits in a bag inside the body and insulin is delivered to the body by a catheter. The insulin glass reservoir can be replaced if empty and the rest of the pump is reusable. The market leader is Metronic.

[0005] 3. Patch pumps: On the market for about 10 years, the entire pump system is disposable for 3 days of use and can be attached to the body like a patch. The market leader is the insulin by Omnipod pump. The use of a pump system has several advantages compared to pen technology: -Far fewer pinholes in the skin, resulting in less pain for the patient Insulin delivery can be controlled and tailored to the specific needs of the patient The pump system can be connected to a glucose sensor system that continuously monitors the glucose level, thereby achieving closed-loop control of the glucose level. Besides insulin, other drugs for increasing glucose levels can be delivered by the pump system. It has many advantages, but also some disadvantages: · The use of the pump cannot be hidden from others, especially in summer. This can stigmatize the patient and may have some social consequences. Although there are advantages to using a patch pump, the use of a pen is the current technology for treating patients in Europe and is the standard of care for diabetic patients, mainly because the cost of a patch pump is much higher compared to pen technology.

[0006] If a patch pump were available that was miniaturized, accurate, and safe on the one hand, and potentially cost-effective in mass production on the other, it would likely become the standard treatment for diabetes. However, there are several challenges to achieving that goal.

[0007] The use of silicon MEMS pumps for diabetes can be considered a promising approach. However, Debiotech (CH) has been continuously focusing on this approach (using silicon MEMS pumps for insulin delivery) for about 25 years, and so far there has been no market breakthrough.

[0008] In current patch pumps, size limitations are imposed on the one hand by the pump system (piston pump technology) and on the other hand by the volume of the reservoir. Therefore, improved approaches are needed. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] European Patent No. 1320727 [Patent Document 2] U.S. Patent No. 8,382,452 [Patent Document 3] International Publication No. 2011 / 107162 Brochure Summary of the Invention [Problem to be solved by the invention]

[0010] It is an object of the present invention to provide a drug delivery system that allows drugs such as insulin or fluids in general to be administered in a manner that has an improved trade-off in terms of utility, precision of the delivered fluid, and cost-effectiveness. [Means for solving the problem]

[0011] This object is solved by the subject matter of the independent claims.

[0012] An embodiment provides a drug delivery system comprising a reservoir having an inlet and a filter. The reservoir can be pre-filled, for example, with a drug / fluid. The system further comprises a measuring device, for example a capacitance measuring device, and a micropump. The reservoir preferably has a serpentine or spiral shape. The micropump is configured to deliver a fluid, such as a drug, from the reservoir to the outlet. The filter is disposed at the inlet and configured to allow air to flow into the reservoir when fluid is delivered from the reservoir.

[0013] The embodiments of the present invention are based on the finding that a reservoir, for example one with a serpentine shape, can be coupled to a capacitance measurement device that allows its improved control. The combination of a capacitive dosing monitoring method that is perfectly adapted to micropumps and allows to detect single pump strokes with sufficient resolution improves the accuracy by significantly delivering the drug. In other words, this means that two main innovations make the difference when compared to the prior art: dosing monitoring and micropump design.

[0014] According to embodiments, a combination of novel micropump technology and novel, accurate and cost-effective medication monitoring technology is provided that can not only resolve every single pump stroke of, for example, 25 nl, but also address safety and reliability topics such as catheter blockage, air bubble recognition, pump failure, reservoir rupture, reservoir fluid level detection, etc.

[0015] According to embodiments, a superior micropump design allows for higher compression ratios, smaller stroke volumes, smaller tip sizes, better air bubble resistance, less capillary adhesion, less van der Waals adhesion, and integrated free-flow stoppage.

[0016] The stroke volume of the microactuator is usually small, while the dead volume of the pump chamber is large, so the compression ratio (corresponding to the ratio of stroke volume to dead volume) of piezoelectrically driven micropumps is also small. One hurdle is the nature of piezo physics, where 80% of the stroke is performed "downwards" by positive voltages, since negative voltage strokes are limited by the depolarization of the piezo. So, in "conventional" piezo-driven micropumps, we are left with a large dead volume and an associated small compression ratio. A big step in micropump performance has been achieved by the Fraunhofer micropump team, where the piezo effect is used during the bonding step to the silicon chip, and after placement, a high voltage is applied to the piezo during curing and released after the glue has hardened, so that when the voltage is released, the piezo is pretensioned "upwards" in a defined way. As a result, the pump chamber height is reduced to very small values, and the large reduction in the dead volume allows micropumps with either very large compression ratios or miniaturization to very small chip sizes.

[0017] Due to the very precise and small stroke volume, the drug delivery system benefits from another advantage: the standard insulin on the market is U100 (i.e. means 100 units in 1 milliliter), which is also used in most patch pumps. 3 ml of U100 insulin is enough for about 3 days. The low concentration of U100 also limits the size of the patch pump. Currently, there are also insulins with higher concentrations available or in development, for example U400, U500, or U1000. In the case of U1000 insulin (1000 units in 1 ml), which has a 10-fold higher concentration compared to U100, the drug volume can be reduced by 10-fold. A 0.3 ml reservoir volume of U1000 is enough for 3 days, and a 1 ml reservoir can deliver to the patient for 10 days.

[0018] For example, each pump stroke, for example 25 nanoliters, can be detected or monitored. The combination of reservoir technology and micropumps from high concentrations of drugs, for example high concentrations of insulin, can be used so that the volume of the reservoir can be reduced. The background is that the introduction of the micropump system makes it possible to deliver volumes smaller than the typical 20 or 25 nanoliters (which is about 1 / 40 of one insulin unit of U1000). Furthermore, the micropump system is so small that it does not contribute significantly to the size (especially the thickness of the patch pump). Thus, the entire drug delivery system can be designed very small and ultra-flat. The drug delivery system can be composed of a reservoir with an inlet, a capacitance measuring device, and a micropump, and therefore consists of few parts, resulting in low complexity and expected manufacturing costs.

[0019] According to an embodiment, the drug delivery system can comprise a needle attached to a micropump. The advantage of the needle combination over the patch-pump system is that the needle is very close to the micropump, which does not have elastic elements and therefore avoids the problems that arise in tubes with small doses. According to an embodiment, the micropump can be placed at the end of the serpentine reservoir or in the middle of the helical reservoir, allowing a very compact design of the entire drug delivery system.

[0020] According to the embodiment, the reservoir can be pre-filled, for example with high concentration insulin. Replaceable reservoirs or fully replaceable drug administration systems can be designed very cost-effectively. Using a spiral or serpentine shape to start the fluid volume allows filling the entire reservoir from one end of the serpentine or spiral track. Considering that during the delivery of the fluid the reservoir is emptied and the fluid is exchanged with air, the serpentine / spiral shape allows only a small part of the inlet to come into contact with air, so that the fluid is not contaminated by air contact. By using an inlet, it is advantageously possible that no negative pressure occurs. Furthermore, when ensuring that the reservoir / drug delivery system is exchanged, for example when 90% of the liquid is delivered, the very small part that was in contact with air is not delivered to the patient. The capacitance measuring device advantageously allows monitoring the fluid level in the reservoir. It is noted that according to the embodiment, the reservoir may be made of glass or polymer, which allows monitoring the fluid level by the capacitance measuring device.

[0021] According to an embodiment, the filter is arranged at the inlet and is configured to allow air to enter the reservoir when fluid is delivered from the reservoir. According to an embodiment, the filter comprises a hydrophobic filter (liquid filter to avoid the ingress of liquids (e.g. in the shower) or an activated carbon filter (gas filter + bacterial filter) or a hydrophobic filter and an activated carbon filter arranged in series. Also other filter types or combinations of other filter types (e.g. with two or more barriers) are possible. For example, as a filter, a passive membrane or mesh, ideally with a very small (0.2 μm) pore size, can be used to ensure sterile filtration of the incoming air. Furthermore, the filter can contain materials such as activated carbon to further remove impurities in the incoming gas. The filter may be in contact with the drug contained in the reservoir and therefore must be compatible with this drug, at least for the innermost filter. Also, three filters, e.g. an outer hydrophobic filter, an inner bacterial filter and a central gas filter, can be used. A combination of filters is also possible. The inner filter may be in contact with the fluid or may avoid contact of the fluid with the other filter. The use of a filter is advantageous since it makes it possible to protect the fluid in the reservoir from contaminated air entering through the inlet of the reservoir. It is noted that the described system with a reservoir with an inlet is not typical. According to an embodiment, the inlet may be equipped with a seal that makes it possible to close the inlet before the pump is attached to the body and used for the first time. The one or more filters make it possible to avoid contamination, for example by bacteria or viruses, from the fluid. Any seal may provide another variant that can be opened manually (for example for the first use). According to an embodiment, a capacitance measuring device makes it possible to determine the state of the inlet (open or closed). It should be noted that the filter may be designed to maintain an external pressure (for example during a dive).

[0022] According to an embodiment, the measurement device may be a capacitance measurement device configured to determine the dielectric constant and / or the capacitance, the dielectric constant and / or the capacitance being for example dependent on the fluid level in the reservoir. According to an embodiment, the system comprises a control device configured to determine the fluid level based on a capacitance signal (change in the capacitance signal) determined by the capacitance measurement device.

[0023] Another possibility to detect the meniscus level in a serpentine reservoir could be an optical sensor or a resistive or magnetic measurement. Thus, the measurement device may be embedded by using optical means. However, the capacitance measurement is the most accurate and cost-effective method.

[0024] According to an embodiment, the system comprises a control device configured to determine a stroke volume during operation of the micropump (pumping using one or more strokes) based on a capacitance signal determined by the capacitance measurement device or based on a change in a fluid level in a reservoir, said fluid level being monitorable using the capacitance signal.

[0025] According to an embodiment, the system comprises a control device configured to determine detection of a fault in the reservoir, e.g., an intrusion, or a fault in the micropump or drug delivery system, e.g., needle dislocation, catheter obstruction, or to detect an open inlet.

[0026] According to an embodiment, the capacitance measuring device comprises a third electrode, which can be attached to the skin, for example, in order to recognize whether the drug delivery system is correctly attached (to the skin). Alternatively, the capacitance measuring device further comprises an electrode with two or more parts, which can be placed in front of and / or behind the micropump, in order to distinguish between drug and bubbles / air / particles and between a fluid or an empty reservoir. Thus, according to an embodiment, each of the two electrodes is separated into two or more parts.

[0027] According to an embodiment, the stroke volume is detected by determining the fluid change during operation of the pump (during one or more pump strokes). If the volume changes / decreases without the pump being operated, it can be concluded that there is a leak in the reservoir (16) or evaporation from the reservoir. If the volume increases, it can be concluded that there is a reflow (from the body to the reservoir).

[0028] It is therefore beneficial to use a capacitance measuring device that allows monitoring of fluid levels, stroke volumes or disturbances. In other words, this means that the capacitance measuring device provides a multifunctional measuring device for drug delivery systems and can be manufactured in a cost-effective manner.

[0029] Optional details of the invention are provided by the dependent claims. Embodiments of the present invention are described below with reference to the accompanying drawings. [Brief description of the drawings]

[0030] [Figure 1] FIG. 1 shows a schematic block diagram of a drug delivery system according to a basic embodiment. [Diagram 2] 1 shows a schematic cross-sectional view of a drug delivery system according to an expanded embodiment. [Diagram 3] FIG. 1 shows a schematic diagram to explain the dependency between the capacitance signal and the fluid level according to an embodiment. [Figure 4a] 1 shows a schematic cross-sectional view of a drug delivery system for explaining in more detail the principle of a capacitance measuring device according to an embodiment; [Figure 4b] 1 shows a schematic cross-sectional view of a drug delivery system for explaining in more detail the principle of a capacitance measuring device according to an embodiment; [Figure 5a] 1 shows a schematic diagram of a drug delivery system according to a further extended embodiment. [Figure 5b] 1 shows a schematic diagram of a drug delivery system according to a further extended embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings, in which objects having the same or similar functions are given the same reference numerals, and therefore the descriptions are interchangeable and mutually applicable.

[0032] Before discussing the embodiments of the present invention, a note on direct concentration is given, which offers the possibility of using small amounts of high concentration drugs instead of large amounts of low concentration drugs. The note is discussed in relation to insulin, but is also valid for other drugs / fluids. This note is given because the reduced reservoir volume can reduce the size of the drug delivery system. However, the use of highly concentrated volumes also brings the need to accurately monitor the volume stroke when reducing the fluid / drug to the basic need to deliver the fluid / drug in very small and / or precise volumes.

[0033] In current patch pumps, size limitations are imposed on the one hand by the pump system (piston pump technology) and on the other hand by the volume of the reservoir. The standard concentration of insulin is U100; i.e., 100 units within 1 milliliter. A reservoir of 3 milliliters of U100 insulin is needed for approximately 3 days of patch pump treatment. There are also higher concentration insulin types available or in development (up to U500 or U1000). A 3ml reservoir of U1000 is sufficient for 30 days of treatment and a 1ml reservoir of U1000 is sufficient for 10 days of treatment.

[0034] Thus, although patch pumps with high insulin concentration and extremely miniaturized pumps are of great advantage to patients, they do present some challenges. U1000 insulin is 1 μl per insulin unit (1 / 1000 ml, so 1 mm 3However, use of U1000 insulin requires a pump system with an exemplary resolution of about 1 / 40 of a unit, implying a volume resolution of 25 nanoliters. Current piston pumps that are cost-effective enough to be incorporated into disposable patch pumps have a volume resolution of 25 nanoliters (1 mm 3 However, it is difficult to achieve a volume resolution of 1 / 40 of that of conventional CT scanners.

[0035] Secondly, if the pump system is capable of administering a volume of 25 nanoliters, there is no dose monitoring technology available to control that this volume is administered. Secondly, the long tubing lengths of several centimeters between the tethered pump and the needle introduce additional dosing errors, as the fluid capacitance of weak components of the tubing or the presence of small air bubbles between the pump and the patient can generate large dosing errors when such small volumes are administered by the pump.

[0036] The conclusion is that if the fluid / drug can be delivered in small volumes and monitored accurately, then a high concentration of drug / volume can be used to reduce the volume of the reservoir. As described with respect to Figure 1, the micropump 12 of the drug delivery system 10 and the capacitance measurement device 14 of the drug delivery stem 10 provide the basis for each.

[0037] 1 shows a drug delivery system 10 comprising a reservoir 16 and a micropump 12. In the reservoir 16 a fluid can be stored, for example insulin (not shown), which can be dispensed by use of the micropump 12. For this purpose, the micropump 12 can be equipped at its outlet with an optional needle 12n. In the reservoir 16 the fluid is stored in a serpentine portion 16m, which extends from an inlet 16i of the reservoir 16 to the micropump 12.

[0038] The drug delivery system 10 further comprises a capacitance measuring device 14. Here, this device 14 is formed by two electrodes 14a, 14b. The electrode 14a is arranged on the upper side (first main surface) of the (flat) reservoir 16 and the electrode 14b is arranged on the lower side (second main surface opposite the first main surface) of the reservoir 16. With this arrangement, the reservoir 16 forms a dielectric with a capacitance 14a+14b. The dielectric constant and therefore the capacitance of the capacitor 14a+14b depends on the fluid in the reservoir 16 or on the meanderings 16m. This principle therefore makes it possible to determine the fluid level in the meanderings 16m. Another possibility is that the changes in the fluid level and therefore the stroke of the micropump 12 delivering the drug can be monitored by using the capacitance measuring device 14. The elongated reservoir volume with the meanderings 16m forms a large area extending along the main surface of the reservoir 16. The area of ​​this region (between electrodes 14a and 14b), and especially the material properties, have a significant effect on the dielectric constant of the capacitor and therefore the capacitance formed by electrodes 14a and 14b. The dielectric constant and capacitance, respectively, depend on the presence / amount of fluid in the meandering section 16m. This configuration allows very good cancellation of capacitance changes due to fluid level changes. For example, this configuration allows determining volume changes due to strokes of, for example, one microliter or less. Furthermore, according to an embodiment, additional disturbance detection mechanisms can be used, for example to detect intrusions and needle dislocations. For example, needle disconnection can result in less bag pressure and therefore less strokes, which can be monitored by the capacitance system 14 described above.

[0039] As mentioned above, the serpentine 16m extends from the inlet 16i to the micropump 12. The inlet 16i has the purpose of allowing fluid to flow into the serpentine to be stored therein. Furthermore, it also allows air to build up in the serpentine 16m when fluid is taken from the reservoir 16, for example by use of the micropump 12, when delivering the fluid. A filter can be arranged at the inlet 16i to avoid the ingress of bacteria or viruses. The filter can have a small pore size. According to an embodiment, the filter can be a hydrophobic filter or an activated carbon filter. According to a further embodiment, a combination of two filters can be used, for example a hydrophobic filter and an activated carbon filter. These two filters can be arranged in series. Of course, according to a further embodiment, it is possible that other filter types can be used, configured to filter bacteria or viruses. As an addition to the filter, a seal can be provided at the inlet. Such a seal prevents the ingress of bacteria or viruses. However, it also prevents the ingestion of air, for example when fluid from the reservoir 16 is to be dispensed by use of the micropump 12.

[0040] According to a further embodiment, the capacitance measuring device may comprise only one electrode attached to the reservoir, eg the skin is used as a counter electrode to determine the dielectric constant (change).

[0041] In the following, optional features according to the embodiments will be described with reference to FIG. 2 shows a drug delivery system 10' for use, for example, as a diabetic patch pump. The system comprises a reservoir 16, a micropump 12, and electrode portions 14a1, 14a2 and 14a3, and 14b1, 14b2 and 14b3. These electrode portions 14a1 to 14b3 form a capacitance measuring device 14. At the inlet 16i, a seal 16s and a filter 16f are arranged, in which, for example, a hydrophobic filter with a pore size of 0.1 μm is implemented.

[0042] At the outlet of the pump 12, a needle 12n is arranged, which allows the drug outlet. This needle 12n is oriented so that it can be attached to the patch 16+12. In the following, the function of the micropump is described. The micropump can be a silicone micropump (3.5 x 3.5 mm2) which generates an airbag pressure of more than 30 kPa. For this, the pump 12 comprises a pump chamber 12c which is actuated using a piezoelectric actuator 12p. At the outlet, a so-called safety valve 12v can be arranged. Of course, it is possible to arrange further valves, for example at the inlet and outlet. The whole pump 12 is covered by a clamp cover 12cc, which is hidden by a silicone gasket 12g. This pump element 12 may be arranged on the upper surface of the reservoir 16.

[0043] The reservoir 16 may be made of glass, i.e. it comprises a bottom glass 16bg and a top glass 16tg. At the sides, the reservoir 16 may be closed by a glass element 16sg. The use of glass is preferred in order not to significantly affect the capacitance measuring device 14. Alternatively, plastic or another non-conductive material may be used. On the top glass 16tg, the pump 12 may be placed, a silicone gasket 12g connecting the two elements 16 and 12. The needle 12n may be fixed by using the glass side element 16sg.

[0044] It should be noted that according to the embodiment, the inlet 16i with the elements 16s and 16f may be arranged on one side of the reservoir 16, while the pump and needle 12n may be arranged on the other side. This allows to have a long trek in the reservoir 16, for example with a serpentine shape, in particular the fluid level in the reservoir 16 can be monitored by using the capacitance measuring device 14. Here, in this embodiment, the capacitance measuring device comprises a first pair 14a1 and 14b1 of three periods of electrodes for seal checking. The main electrodes 14a1 and 14b2 are for fluid level monitoring and the third pair 14a3 and 14b3 are for fluid level detection.

[0045] The structure of the drug delivery system 10' is discussed, and the functional principles and components of the system 10' are discussed. When the micropump 12 is actuated to make a single stroke volume (e.g., 20 nanoliters), the meniscus is moving forward and finally the insulin is displaced by air (see inlet 16i). Because insulin has a much higher dielectric constant than air, the capacitance decreases. This capacitance decrease can be accurately detected by electronics (not shown). This dependency is illustrated in Figure 3.

[0046] FIG. 3 shows a diagram of the capacitance c(x) plotted against the meandering position x. Here, fully and x emty C fully and c empty As can be seen by the enlarged view, the curve, which has a substantially linear dependence in the smaller view, contains steps. These steps result from a single pump step. With reference to Fig. 4a, Fig. 4b, the background of the detection of the correction position is shown.

[0047] Figure 4a shows the system 10' attached to the body 20. As can be seen, the needle 12n extends into the body 20. Figure 4a shows the fluid level (and seal level 15) in the reservoir 16 before a stroke, and Figure 4b shows the fluid level 15' after a stroke.

[0048] The stroke volume dv follows the insulin delivered into the body 20. As can be seen by FIG. 4b, the stroke volume dv is marked at two locations, namely next to the needle 12n as the insulin delivered into the body 20 and next to the inlet 16i as the missing insulin level in the reservoir 16. This portion marked as stroke volume dv in the reservoir 16 as well as the portion with fluid 15' are monitored using the electrodes 14 and 14b2. As mentioned above, insulin has a different dielectric constant when compared to air. Due to the fact that air replaces insulin in the portion indicated by the stroke volume dv in the reservoir 16, the capacitance is changing. This capacitance change dc is marked. This capacitance change allows the meandering position to be determined using the capacitance measuring device 14.

[0049] Air inlet 16i protects medication 15 / 15' as described below. The meniscus can only move without disturbance if no negative pressure is generated by this movement at the inlet. The principle requires a connection to the ambient air at the inlet of the serpentine. At the end of the serpentine, the drug comes into contact with the ambient air. The drug can be contaminated by any kind of undesirable substance, such as bacteria, viruses, poison molecules, etc. To avoid that contamination, the following strategies are chosen: A hydrophobic filter 16f with a small pore size (e.g. 0, 2 μm) protects the inlet. These types of filters have a high bubble point, due to the small pore size, where pressures of more than 10 bar are required to pressurize the liquid through the filter. Therefore, none of the liquid that is not bacteria or viruses can enter the inlet. Additionally, an activated carbon filter 16f is placed in series with the hydrophobic filter to prevent undesirable gaseous molecules such as hydrocarbons from entering the inlet and coming into contact with the drug at the end of the serpentine. The serpentine shaped drug reservoir 16 is pre-filled with drug. The inlet 16i is protected by a filter with small pore size and activated charcoal 16f, as well as by a seal that is an air-tight closure of the inlet. Therefore, the filter is usually installed after filling.

[0050] For that purpose, before the patient uses the patch pump, the drug is sealed from the environment, even from the air. When the patient uses the patch pump, the patient removes the seal. Starting from that time (seal removal), the ends of the serpentine have pressure contact with the environment and can move when the micropump is pumping. o For safety reasons, the system control can detect if the seal has been removed (e.g. also by a capacitance sensor, if the capacitance changes, when the seal is removed).

[0051] It must be mentioned that even if undesired gaseous molecules could pass all the filters 16f and come into contact with the drug 15, they would be resolved at the end of the serpentine, which has a length of about 100 millimeters (depending on the cross section of the channel and the desired total drug volume in the reservoir). The diffusion time of that molecule is very long compared to the use time of the patch pump (about 7 days). Then, to further reduce this risk, the patch pump should use only 80...90% of the drug, and the end of the serpentine, where there may be some contamination, would never be administered to the patient.

[0052] According to the embodiment, the cross section of the track ranges from 0, 5 mm to 3 mm, preferably 1 or 2 mm. The value chosen depends on the characteristics of the fluid, the smaller the cross section of the tack allows a more accurate determination of the fluid level. The background is that fluid changes result in large strokes along the serpentine track. It should be noted that the friction between the fluid and the track depends on the channel cross section.

[0053] Regarding the serpentine 16m in the reservoir 16, it should be noted that its shape is not important. The track can have a substantially square or circular shape, or can taper from the inlet 16i to the outlet 12m. Also, instead of a serpentine, a spiral shape can be used. Here, the so-called "LifeCoin" patch pump can be found. With a slight modification to use a spiral instead of a serpentine and to place the pump 12 in the center of the spiral, a LifeCoin can be formed.

[0054] The LifeCoin is pre-filled with insulin and the serpentine spiral is made from clay or plastic. The air inlet and needle outlet are covered by airtight seals that are removed by the patient before inserting the coin into the body.

[0055] The LifeCoin as well as the serpentine-shaped drug delivery system 10' preferably comprises a special electrode design, here for example a capacitance measuring device in front of the three electrode parts, which allows control and monitoring of the system. For example, the design can be made to allow the resolution of the signal stroke, as explained with respect to Figs. 4a and 4b. Furthermore, according to the embodiment, additional system control elements can be integrated, for example a controller for the actuation, dosing control and / or regulation of the pump 12 / 12p. Furthermore, preferably the patch pump comprises a battery, which is not shown in the above embodiment. An additional sensor, such as a glucose sensor, may optionally be integrated on or in or behind the needle 12a. This allows the connection of a closed-loop artificial pancreas with a glucose sensor.

[0056] In that case (if the glucose sensor is adjusted in the needle 12a), no wired data transmission (e.g. Bluetooth) is required to control the glucose level by adjusting the insulin administration rate by the micropump. The system control can not only monitor the insulin pumping rate and detect pump failures, but also adjust the blood glucose level by an appropriate control algorithm.

[0057] The whole system is very compact, flat, small and operates independently to control blood glucose level. In that case, there is only a small display and / or alarm signal possibility (acoustic, optical) to inform and indicate the status of the working drug delivery system to the patient. Thus, the independent operation can be configured without wires and data transmission units (which require a lot of energy, shorten the wearing time or require large batteries).

[0058] It should be noted that the system can be operated with a small amount of energy. Here is a short consideration of the energy requirements of a micropump:2 The capacitance of is about C = 1.5nF and the voltage level (peak is 100V). To deliver 1ml of reservoir, N = 50000 pump strokes are needed to empty the reservoir, according to 1000000nl. The efficiency of the electronics for generating the voltage is assumed to be just η = 30% (low efficiency due to the small voltage of the proposed flat battery).

[0059] In the following, the amount of energy is exemplarily calculated: for example, the total energy required by a micropump is E=N / η*1 / 2C U 2 Therefore, the total energy required for the pump is E = 2.5 Joules.

[0060] For comparison, commercially available button cells have a typical end-of-life voltage of about 1.5V to 2V and a capacitance starting at about 5mAh. The button cell energy generator 750 is sized D5.7mm x 1mm and can store up to 36J of energy. (The low continuous discharge current of these batteries (usually about 1mA) can be stored in a capacitor, which is used to power the electronics only during pump / sensor operation.) Also, flat lithium batteries, e.g. 1 x 12 x 12mm 3 A GEB201212C battery having a size of 1.0 mm, a voltage rating of 3.6 V and a capacity of 10 mAh (=130 mJ) can be used.

[0061] It should be noted that the drug delivery system should be in "sleep mode" for almost the entire time, only waking up while the desired amount of insulin has to be pumped, which allows for longer battery life. According to further embodiments, other drugs can be delivered instead of insulin, such as hormones, monoclonal antibodies or painkillers. According to further embodiments, the design of the pump 12 together with the reservoir 16 may have a flow restriction or a free flow stop as a free flow stop. For this, the safety valve 12v may be important. Furthermore, the seal protects the device during storage.

[0062] In the following, further features and in particular advantages of the patch pump 10' are described. According to an embodiment, this patch pump is on the one hand much smaller compared to the prior art. It is so small that it can be placed behind a shirt without being recognized by anyone else. It should be noted that the patch pump is very precise in dosing. Every pump stroke (e.g. 3.5 x 3.5 x 0.6 mm for 20 nanoliters) is very precise. 3 The silicon micropump) can be resolved by electronics, so even accurate single-stroke monitoring is possible. For example, the patch pump can perform any bolus required for the patient and is fully programmable.

[0063] According to the embodiment, the patch pump knows exactly the insulin filling status and can tell the user exactly about the remaining insulin until the next exchange. It should be noted that even several patch pump systems can be stacked on top of each other or in the same plane, each patch pump having a separate micropump, in case it is necessary that the patient does not need only one drug due to the small size. For diabetic patients, there are times when it is necessary to lower the blood glucose level with insulin or to raise it with another drug. A further embodiment allows evaporation of the drug, and depending on the vapor pressure of the drug, there is a slight evaporation at the end of the meniscus through the inlet and the filter. This evaporation can be reduced if a long air channel (diffusion stop) with a small cross section (much smaller compared to the cross section of the serpentine channel where the drug is) is placed between the inlet and the start of the drug. This will result in a saturated atmosphere with drug molecules at the meniscus and the evaporation will be very small. Due to the long channel, the drug molecules have a long distance towards the inlet and the channel acts as a diffusion barrier. The advantage is that this patch pump is very safe. Catheter blockage, pump failure, needle dislocation, air bubble ingress, glass breakage, all these failure modes can be easily and quickly detected by the electronics. Further embodiments for fault detection include: Pump failure (operation): If the pump should perform one pump stroke and the meniscus does not move, the capacitance does not change => failure Pump failure (valve): If the pump should perform one pump stroke and the meniscus does not move, the capacitance does not change => failure Catheter obstruction: if the catheter is obstructed, the pump cannot push the drug forward and the meniscus cannot move => failure By having separate electrodes on the bottom of the housing, the system is able to know if the patch pump is attached to the skin or not. The system only starts to function if the patch pump is attached and remains attached. With one separate safety electrode (e.g. placed just before or just after the micropump) air bubbles can be easily detected because the electrode can distinguish between drug and air bubbles. In normal case, at this electrode, air bubbles should never be present. If the safety electrode detects air bubbles => fault Glass breakage or reservoir breakage: In that case the capacitance is changing rapidly: => failure

[0064] Regarding costs, it is noted that the smallest silicon micropump today has a chip size of 3.5x3.5mm2 and a stroke volume of 20 nanoliters. With a production rate of 200 wafers per week, the manufacturing costs of the tested pump chips seem feasible in the long term of less than 40 cents. Assuming that all electronic components can be placed in one or two specific ASICs. Together with a reasonable flat battery manufacturing cost (without insulin) of 2...3 euros can be achieved in the long term in very large volumes, which could be a game changer for that market.

[0065] The above-mentioned lifecoin is described with reference to Figures 5a and 5b. Figure 5a shows a side / cross-section view of a lifeCoin 10'' and 5b shows a top view of the lifecoin 10''. The LifeCoin has a substantially round shape, with most of the area (see Figure 5b) being used by the reservoir 16''. In this embodiment, the reservoir 6'' comprises a track in which a fluid can be stored, the track having for example a spiral shape extending from the outside to the center. The start of the spiral is marked by 16i'' representing the inlet and the spiral ends in a micropump 12 placed in the center of the spiral. As can be seen, a needle 12n is attached to the bottom side of the unit 10''.

[0066] The components may be substantially similar to the embodiments described in the context of Figures 1 and 2 and may include some optional features. In this embodiment, the reservoir 16'' comprises a solid metal or plastic cover on top of which the micropump and further elements such as wireless communication (Bluetooth) elements 22, a battery 24 or a controller 26 (here an ASIC for the micropump, sensor reading and / or dose monitoring) may be located. The needle 12n on the button side of the reservoir 16'' may include a seal.

[0067] It should be noted that in terms of size, the entire system 10'' can have a diameter of 30 mm or 40 mm (ranging from 20 mm to 60 mm) and a thickness of 4 to 5 mm, allowing the reservoir 10'' to store 1 ml of insulin. With regard to inlet 16i'', it is mentioned that this is combined with two filters 16f1'' (activated current filter) and 16f2'' (0.2 μm hydrophobic filter), and a seal for the air inlet 16s'' may be attached, for example, to the top surface of unit 10''.

[0068] In the following, an exemplary design of this lifecoin10'' is described, with a special focus on the capacitance measurement device. The change in capacitance for one single pump step is: TIFF2025060981000002.tif11124Using the following parameters: ΔV: Pump stroke volume: 20nl (3.5×3.5×0.6mm 3 Silicon Micro Pump) · TIFF2025060981000003.tif44Dielectric constant: 8.85e-12 · TIFF2025060981000004.tif414 Dielectric constant of insulin: about 35 (depends on insulin) · TIFF2025060981000005.tif412 Dielectric constant of cover (glass): 7 (depends on the type of glass) H channel: Insulin channel height: 1.5mm H cover Height of both covers (glass): 0.6mm ·W channel Insulin channel width: 1.5mm ·W wall Glass wall width: 0.3mm Reservoir volume: 1ml

[0069] Note that these parameters are assumed for illustrative purposes only. This gives: Capacitance change per pump stroke (20nl): 843aF · Digital steps of (conventional) capacitance to digital converter for one pump stroke (20 nl): 14 steps: thereby a single pump stroke can be easily solved. Total pump strokes in reservoir: 50,000 pump strokes Total Capacitance Change: 42pF I channel : Spiral length: 44.4mm In this data, the coin has a diameter of 3.2 cm.

[0070] It can be seen that the capacitance change of one pump stroke depends on the height of the drug (e.g., insulin and / or glucagon) channel. A decrease in height leads to an increase in its capacitance change (if all other parameters are constant). For example, when the height is decreased from 1.5 mm to 0.75 mm, the capacitance change of one pump stroke of 20 nanoliters increases from 843 aF to 1920 aF (with about 31 digital steps of a typical commercial CDC converter / pump stroke), while a decrease in height to 0.5 mm results in a capacitance change of 2940 aF (with 48 digital steps / pump stroke). That is, a reduction in the channel height is a way to increase the sensitivity of the stroke volume measurement.

[0071] The channel height is a suitable parameter for tuning the sensitivity of the stroke volume measurement. Secondly, as the channel height decreases, the capillary forces that hold the meniscus in a stable position (largely independent of gravity) increase.

[0072] On the other hand, there are also drawbacks to making the channel height smaller, in particular the length of the channel must be increased to achieve a certain drug reservoir volume (e.g., 1 ml for U1000). This increase in channel length has the following drawbacks: 1) For a 1 ml reservoir (and 1 mm wall thickness between channels), the lateral space of the reservoir would need to increase from 3.8 cm (1.5 mm channel height) to 5.3 cm (0.75 mm channel height) to 6.5 cm (0.5 mm channel height) coin diameter for the spiral reservoir. 2) As the channel height decreases, the friction to move the meniscus increases rapidly according to the law of laminar friction when the pump is operating.

[0073] This can be partially improved if the width of the channel is increased, for example from 1.5 mm to 2 mm or 3 mm, but the width must not be too large to guarantee a defined movement of the meniscus when the pump is activated. So, looking at the 1 ml reservoir size of U1000 insulin, a channel height of 1 mm or 1.5 mm could be a good compromise between capacitance stability resolution, meniscus stability, lateral size of the reservoir, and laminar friction of the moving liquid in the channel.

[0074] For other reservoir sizes (e.g., 0.3 ml reservoirs), smaller channel heights or other geometries may be better suited to accommodate other geometries. In the future, when new high concentration drugs may be developed, even smaller reservoir sizes, for example 0.1 ml or less, may be used, in which case the channel height can be further reduced to values ​​of 0.5 mm or 0.1 mm, and the capacitance signal will be even higher, allowing for precise dosing of very small volumes (e.g., 10 nanoliters or less than 1 nanoliter) by future micropumps with stroke volumes smaller than 20 nanoliters.

[0075] According to an embodiment, the cross section of at least one dimension will be 2.8 mm or 3 mm or less, for example 3 mm x 3 mm or 2.8 x 2.8 or 4 mm x 2 mm or preferably 1.5 mm x 1.5 mm or 2 mm x 1.5 mm or 1.5 mm x 1 mm, etc., where at least one dimension must be less than 3 or 2.8 mm to maintain a meniscus in the reservoir. Consider the background based on the following formula: JPEG2025060981000006.jpg4584

[0076] Here, the interfacial surface energy σ is defined as σ=dE / dA=dF / ds. σ Wasser-Luft is the interfacial surface energy between water and air. 2.8 mm is valid for water surrounded by air. Based on this calculation, it can be concluded that for small structures (less than 2.8 mm in at least one dimension), the interfacial surface force is greater than gravity, so the meniscus is maintained. At least one dimension can be smaller than 2.0 mm or 1.5 mm, for example, to have a reserve in case of shaking.

[0077] According to an embodiment, lifecoin'' may be implemented as a closed loop system, e.g., an artificial pancreas within lifecoin: With the use of modern real-time glucose sensors (e.g. Dexcom G6), lifecoin will become a closed-loop system, allowing diabetics to lead a normal life without constantly worrying about glucose measurements. The sensing element may be integrated directly into the Lifecoin (although only in one device, the insulin administration area) or connected via wireless communication. With tailored control algorithms (e.g. AI) a safe and comfortable solution for diabetic patients can be provided. The same principle could work for other chronic diseases for which sensors are available.

[0078] In the following, the electrode design and function will be described, where an optional element of this capacitance measuring device should be mentioned. The capacitance measuring device may be arranged as electrodes arranged on the top and bottom surfaces of the reservoir 16'', but is not shown in the diagrams of Figures 5a and 5b. For capacitance measurements, different electrode configurations are possible: the standard approach consists of two parallel electrodes at the top and bottom of the reservoir 16r (common parallel plate capacitor design).

[0079] Another exemplary possibility is two coplanar electrodes on only one side of the reservoir 16''. This design is potentially cheaper to manufacture, but requires more complex methods for electronic field calculations and disturbance avoidance (e.g., GND electrode shielding designs). Regardless of the electrode configuration selected, it is possible to use multiple electrodes to divide the reservoir into multiple sub-areas, or to use two electrodes in parallel to obtain a dual control measurement of the reservoir level.

[0080] Capacitance measurement is a key component of the lifecoin design 10''. In theory, it is possible to detect capacitance changes even with a single pump stroke. In practice, there are many external and internal disturbances that can prevent accurate capacitance measurements: capacitance changes due to temperature or external E-fields, interference with "patient ground / patient noise", and sensor drift. To compensate for these effects, precautions can be taken: · Shielding the measuring electrodes from external disturbances by using top / bottom covering shields; providing a disturbance measurement and estimation means, e.g. dedicated "static" electrodes used for drift correction; and Uses a "zero before actuation" strategy where the capacitance is set to zero just before pump actuation to eliminate drift effects A typical CDC chip has multiple capacitance measurement channels. Most channels will most likely be used for liquid level detection, but some can be utilized to obtain additional functionality. Dedicated electrodes can be used, for example, for: Air bubble detection Drift detection and compensation Fluid dielectric sensing (electrodes with precisely defined area and distance), this can even make it possible to check whether the used insulin has been spoiled (if the pre-filled unit is stored for a longer time or exposed to radiation etc.) Post-pump meniscus movement detection (to allow for automatic filling when the patient unpacks the system) Detects when seals / outer covers are removed

[0081] According to an embodiment, a modular design for improved sustainability can be used. By using a modular system design, it is possible to build a more sustainable and possibly cheaper lifecoin. In this approach, the electronics (pump driver circuit 26, battery 24, CDC IC 36) are separated from the fluids (serpentine with electrodes, pump and needle). The pump itself is part of the disposable component, so no complex fluidic / mechanical interface between these two subsystems is needed. The only connections used between the electronics and the fluidic components are some additional electrical tracks connecting the CDC chip 26 and the electrodes on the fluidic reservoir 16r, and the (two) electrical connections between the micropump 12 and the pump driver 26.

[0082] This is a major difference (and possible advantage) over "syringe / plunger type" administration systems, where changing the reservoir always involves an initial filling step to bring the plunger into contact with the new reservoir, and during this step the system may lose some drug or overdose the patient.

[0083] Modular designs can eliminate expensive electronic components, thus reducing waste and potentially lowering the overall system cost. Using a modular design, additional functionality can be realized, for example the needle can be automatically mechanically advanced when electronic components are attached. The entire system can maintain its very flat shape even with its modular design.

[0084] Furthermore, it should be noted that for channel manufacturing, the following tolerance calculations can be taken into account: How does the (calculated) pump volume change depend on the variation of other parameters (e.g. channel height): TIFF2025060981000007.tif12141Qualitative Considerations:h channel Since h exists in square form in the formula, channel Variation in θ doubles the error in stroke volume.

[0085] Assuming a 10% repeatability (without individual calibration of the LifeCoin), the tolerance on the channel height should not exceed 2-3%. This is true for the variants on the glass cover as well. The permittivity and capacitance exist only in linear form, so that a tolerance of about 4-6% is allowed for these parameters. (All contributions are squared and summed in relation to the square root.) If the channel height is 1 mm and the cover thickness is 0.3 mm (as in the previous example), the channel height should not vary by more than 20 μm to 30 μm, and the cover thickness should not vary by more than 6 μm to 9 μm.

[0086] The strength of the variation in the dielectric constant depends on the manufacturing method of the insulin. It is envisaged here that this parameter is measured for each batch and transferred to the system controller. From the above considerations, it seems clear to use a glass plate with a highly defined thickness and then completely mold the serpentine spiral. This involves using two covers with highly defined thickness. The spiral is capped by gluing using these two (patterned) covers. The covers then comprise through-paths for insulin at the inlet and outlet.

[0087] It should be noted that according to an embodiment, it is advantageous to use a "brick" reservoir such as glass for safety and free-flow protection. The advantage of a glass structure is that it is difficult for the user to create an overdose by exerting force on the reservoir, whereas in the case of a flexible bag, which can deform, overpressure cannot be created, which entails the risk of overdosing, and a glass reservoir would break.

[0088] The only danger required is the situation when the patient is close to the ground in a plane: the body needs to take several breaths to compensate for the pressure, resulting in a slight difference in pressure. This pressure difference can cause a slight overdose. The dangers are, for example: For example, if a patient is suddenly placed in a hyperbaric chamber and given artificial ventilation using an oxygen tank, Or if overpressure is intentionally created with a LifeCoin, for example by placing a bell jar over the LifeCoin and pumping it. The result will be free flow.

[0089] Regarding free-flow protection, embodiment according to variant 1: this potential malfunction can be avoided using a safety valve 12v (e.g. using the known FhG patent of 2007, as shown in FIG. 2). This safety valve is preferably integrated into the silicon pump chip. It is configured such that the maximum free-flow leakage rate during a (possible) false overpressure is less than or equal to the bolus rate of the application.

[0090] Embodiment according to variant 2: A flow restriction (in the pump silicon or in the reservoir serpentine (glass or plastic)) configured to not administer a harmful dose even in the worst case overpressure (on an airplane or in case of deliberate overpressure) may be sufficient. This restriction may be a narrow cross section in the path of the drug. According to an embodiment, the flow restriction may be implemented as a filter immediately prior to the pump to protect the pump from insulin crystals or other contamination. Note that depending on the risk assessment, a safety valve may be beneficial.

[0091] According to an embodiment, disturbance parameter detection can be performed as follows: A constant skin temperature of approximately 32° always results in similar viscosity characteristics of the medium. If the pump does not degrade (or degradation is definable) over a short application period, more pump strokes are used for the same delivery volume, so that changes in the medium viscosity (-> insulin degradation) can be detected, or clogging of the fluid line (-> occlusion or extravasation) can be detected. Detection of different types of insulin using different dielectric constants and, consequently, matching capacitances and delivery rates (as well as recognizing that U1000 insulin has been mistakenly used instead of U100 insulin)

[0092] Regarding the electrode design, it should be noted that according to further embodiments, one or more of the following principles can be used: Finger electrodes following the meanders to reduce the total capacitance and the "stray capacitance" caused by the channel walls Use of planar "single-sided" electrodes with no counter electrode for ease of manufacturing Here, a new capacitance calculation can be used: plates adjacent to each other instead of opposite each other, etc... or... otherwise, more difficult constellations (especially with different E R ) simulation is used. Shielding from ground (patient's skin) at the underside / bottom of the patient to keep the effects of external disturbances low o There may always be a dedicated drift detection electrode in the fluid filled area (and another drift detection electrode in the completely free area) so that drift can be better subtracted Subdivision into several electrodes so that several channels of the measurement IC can be used Either one provides a partial electrode (like 1 electrode per 20% of the channel length = 5 electrodes -> divides the total capacitance) Or two (or more) parallel electrodes that monitor themselves or each other's fill level Other electrodes can be used to detect seal ripping. Additional electrodes are located behind the pump (and / or near the needle) o Determining when the pump is filled (either at the patient or at the factory when pre-filling the reservoir) o Detection of bodily fluids if reflux occurs (bodily fluids have a different dielectric constant compared to insulin) Starting from this electrode, there is a precisely defined volume (of the syringe) before the meniscus reaches the patient

[0093] Regarding the modular design, it should be noted that according to embodiments, further cost savings are possible when designing the electronics (pump driver, battery, and possibly capacitive IC) to be separable. They do not come into contact with the patient / insulin and can be reused. Disadvantageously, it consumes slightly more space, but is more sustainable.

[0094] Note that additional flow restrictions are placed in the fluid-containing portion of the flow path: Additional safety in case overpressure in the reservoir occurs for any reason (lower flow rate) Hardly interferes with pump action due to low frequency effect: at the same time it protects the pump from crystals / particles in the insulin and is fail-safe: if air is sucked in it is trapped in the filter.

[0095] Concerning the surface properties, it is noted that according to embodiments, a (idle) net angle of 90 degrees (generally ranging from 75° to 105° or 60° to 120° or 45° to 135°) between the insulin and the channel can be used for the best meniscus formation. The background is that evaporation / condensation effects can affect the sensor resolution, especially over days to weeks. The above mentioned wetting angles of 90 degrees or sometimes around 90 degrees, 75 to 105 degrees can be used. Concerning the sensor drift, it is noted that according to embodiments, the known concept of "zeroing before actuation" can be applied to minimize drift effects.

[0096] Regarding the shape of the serpentine / spiral / track cross section: the shape of the cross section will affect whether insulin will remain in the corners. A circular or elliptical shape is best, but can be difficult to manufacture. Thus, according to an embodiment, rounded edges are preferred. However, even if insulin remains in a sharp corner of the cross section (e.g. rectangular cross section), this can be addressed: if the insulin remaining in the sharp corners is constant, this can be considered a constant offset.

[0097] Furthermore, according to the embodiment, the inner surface of the serpentine channel may be smooth. If the roughness is too large, the meniscus must change shape at this fine roughness depending on the wetting angle by advancing. This change in shape is similar to a (small) capillary pressure and may affect the accuracy and reproducibility of the measurement of a single pump stroke. If the roughness is small enough (e.g. less than 1 μm), the meniscus can advance without having significant obstacles.

[0098] However, even with larger roughness, the capacitive dosing monitoring still works and only single pump stroke measurement variations occur. Over a volume of 50 pump strokes of a 20 nanoliter silicon micropump to achieve 1 unit of U1000 (by 1 μl), the error du versus surface roughness should not be significant.

[0099] The process for connecting the drug delivery system to the patient can be supported by additional devices. To ensure the connection reliably, some kind of needle is used to penetrate the outer skin into the deeper area and remain there. To reduce stress from the rigid needle, the needle is usually only used for penetration and then rejected leaving only the non-rigid administration end inside the body. For this procedure, certain devices are preferred. Continuous blood glucose sensors use a handheld device that the patient places on the skin, presses a button, and inserts the drug delivery tube while the needle adheres the patch on the skin. The sensor electronics are then clicked onto the patch and the sensor is ready to operate.

[0100] A similar system can be envisaged for the drug delivery system described here above: the fluidic part is glued to the skin while injecting the drug delivery tube. All fluidic components are already in place (no open areas where contamination can occur) and the (reusable) electrical components (battery, pump driver, transmitter and logic) are inserted afterwards. A tensioned spring releases the needle after pressing the button, opening the skin for the microtube connected to the micropump outlet (and initially to the needle). While the needle immediately retracts, the microtube loses its connection and remains under the skin.

[0101] According to an embodiment, the drug delivery system can comprise two reservoirs (side by side, layer by layer, or combined) for two different drugs. For example, the drug delivery system consists of two lifecoins, one filled by insulin and one by glucagon (a hormone opposite to insulin). The first method ensures to keep blood glucose low, while the latter method stops the action of insulin if blood glucose reaches a dangerously low range. This can happen by the patient playing sports or skipping meals. Using both the pump and the glucose sensor, a real artificial pancreas can be created (this is already done by other pumps). Glucagon is also available in cheap small cartridges and can be handled similarly to insulin. Controlling which drug is delivered can be done by a controller connected to the glucose sensor.

[0102] Instead of two lifecoins, a system can be realised with two separate serpentine shaped reservoirs in one layer (one filled with insulin and one filled with glucagon), each reservoir with one micropump to deliver either insulin or glucagon independently. Both pumps can be placed in the centre of the coin. In this embodiment, either two different needles or catheters can be attached to deliver either insulin or glucagon, or within the lifecoin channel system there is a Y-junction between the outlets of the two pumps and the outlet to the needle, where the drug (either insulin or glucagon) is delivered.

[0103] To save on manufacturing and / or packaging costs, two micropumps (e.g., the 3.5 mm 2 The silicon micropumps are diced together from the wafer (size 3.5 × 7 mm) (both pumps have integral safety valves). 2 ), which can be attached (eg, glued) to a channel system (with two meanders for insulin and glucagon).

[0104] Although some aspects have been described in the context of an apparatus, it will be apparent that these aspects also represent a description of a corresponding method, with a block or apparatus corresponding to a method step or a feature of a method step. Similarly, aspects described in the context of a method step also represent a description of a corresponding block or item or function of a corresponding apparatus. Some or all of the method steps can be performed by (or using) a hardware apparatus, such as, for example, a microprocessor, a programmable computer, or an electronic circuit. In some embodiments, some of the most important method steps can be performed by such an apparatus.

[0105] Depending on specific implementation requirements, embodiments of the present invention can be implemented in hardware or software. Implementation can be done using digital storage media, such as, for example, ROM, PROM, EPROM, EEPROM or flash memory, in which electronically readable control signals are stored and which cooperate (or can cooperate) with a programmable computer system to execute the respective method. Thus, the digital storage media can be computer readable.

[0106] Some embodiments of the present invention comprise a data carrier having electronically readable control signals capable of cooperating with a programmable computer system to cause one of the methods described herein to be performed.

[0107] Generally, embodiments of the present invention can be implemented as a computer program product comprising program code which operates to perform one of the methods when the computer program product is run on a computer. The program code may for example be stored on a machine readable carrier.

[0108] Other embodiments comprise the computer program for performing one of the methods described herein (determining a disturbance and controlling a pump in response to, for example, a sensor signal or an external command), stored on a machine readable carrier. In other words, an embodiment of the inventive method is, therefore, a computer program having a program code for performing one of the methods described herein, when the computer program runs on a computer.

[0109] In some embodiments, a programmable logic device (e.g., a field programmable gate array) may be used to perform some or all of the functions of the methods described herein. In some embodiments, a field programmable gate array may cooperate with a microprocessor to perform one of the methods described herein. In general, the methods are preferably performed by any hardware apparatus.

[0110] The above-described embodiments merely exemplify the principles of the present invention. It is understood that modifications and variations of the configurations and details described herein will be apparent to those skilled in the art. It is therefore intended to be limited only by the scope of the appended claims and not by the specific details presented as illustrative and explanatory of the embodiments herein.

Claims

1. A drug delivery system (10, 10', 10'') comprising: At least one reservoir (16) having a serpentine (16m) or helical shape, the reservoir (16) comprising an inlet (16i) and a filter (16f); a measurement device (14) configured to determine a parameter of the at least one reservoir (16); at least one micropump (12) configured to deliver fluid from the reservoir (16) to an outlet; The filter (16f) is disposed at the inlet (16i) and configured to allow air to enter the reservoir (16) when the fluid is delivered from the reservoir (16).

2. The drug delivery system (10, 10', 10'') of claim 1, wherein the reservoir (16) is pre-filled with a fluid or drug.

3. 3. The drug delivery system (10, 10', 10'') according to claim 1 or 2, wherein the filter (16f) comprises a hydrophobic filter (16f) or an activated carbon filter (16f) or a hydrophobic filter (16f) and an activated carbon filter (16f) arranged in series, or another filter or combination of filters configured to filter viruses and / or bacteria.

4. The drug delivery system (10, 10', 10'') according to any one of claims 1 to 3, wherein the inlet (16i) is provided with a seal (16s).

5. the housing of the reservoir (16) is made of glass or a polymer; and / or The drug delivery system (10, 10', 10'') according to any one of claims 1 to 4, wherein the serpentine (16m) or spiral shape comprises a track extending from the inlet (16i) to an opening for the micropump (12).

6. 6. The drug delivery system (10, 10', 10'') according to any one of claims 1 to 5, wherein the measurement device (14) is implemented as a capacitance measurement device (14) and / or comprises one electrode arranged on a side of the reservoir (16) with the reservoir (16) and / or the fluid therein acting as a dielectric, or two electrodes (14a, 14b) arranged on either side of the reservoir (16) with the reservoir (16) and / or the fluid therein acting as a dielectric.

7. The drug delivery system (10, 10', 10'') of claim 6, wherein each of the two electrodes (14a, 14b) is separated into two or more parts, or each of the two electrodes (14a, 14b) is separated into two or more parts to increase the resolution for detecting fluid levels or determining disturbances.

8. The drug delivery system (10, 10', 10'') of claim 6 or 7, wherein the capacitance measuring device (14) is configured to determine a dielectric constant and / or a capacitance, the dielectric constant and / or the capacitance being dependent on a fluid level in the reservoir (16).

9. The drug delivery system (10, 10', 10'') according to any one of claims 6 to 8, further comprising a control device configured to determine the fluid level based on a capacitance signal determined by the capacitance measurement device (14).

10. a control device configured to determine a stroke volume during operation of the micropump based on a capacitance signal or a change in the capacitance signal determined by the capacitance measurement device, or A drug delivery system (10, 10', 10'') as claimed in any one of claims 6 to 9, further comprising a control device configured to determine a stroke volume based on a capacitance signal or a change in capacitance signal determined by the capacitance measurement device (14) during operation of the micropump to deliver a fluid using a single stroke or multiple strokes.

11. The drug delivery system (10, 10', 10'') of any one of claims 1 to 10, further comprising a control device configured to determine a disturbance in the reservoir (16) or a disturbance in the micropump (12) or a disturbance in the drug delivery system (10, 10', 10''), or to detect an open inlet (16i), or to determine partial closure or occlusion of a needle (12n) or a tube, to determine air or particles in the reservoir (16), or to determine a leak in or evaporation from the reservoir (16), or to determine backflow.

12. the capacitance measuring device (14) comprises a third electrode (14a, 14b) attachable to the skin in order to recognize whether the drug delivery system (10, 10', 10'') is correctly attached to the skin; and / or A drug delivery system (10, 10', 10'') according to any one of claims 6 to 11, wherein the electrode of the capacitance measuring device (14) comprises at least two portions arranged in front of and / or behind the micropump (12) to distinguish between drug and air bubbles.

13. a second reservoir (16) in combination with a second micropump (12) or a second reservoir (16) for delivering another fluid from the second reservoir (16) to an outlet; A drug delivery system (10, 10', 10'') comprising a second reservoir (16) formed as a further meander or spiral along with or adjacent to the meandering spiral for delivering another fluid from the second reservoir (16) to an outlet.

14. The drug delivery system (10, 10', 10'') according to any one of claims 1 to 13, wherein a needle (12n), catheter or tube is attached to said outlet.

15. or a glucose sensor in contact with the body fluids via its own catheter or via a needle (12n), catheter or tube of said drug delivery system (10, 10', 10''); A drug delivery system (10, 10', 10'') as described in any one of claims 1 to 14, further comprising a sensor or glucose sensor in combination with a control device, contacting a body fluid via its own catheter or via a needle (12n), catheter or tube of the drug delivery system (10, 10', 10'').

Images