HK40017210A - Medical sensor system, in particular continuous glucose monitoring system - Google Patents

Description

Medical sensor system, in particular continuous glucose monitoring system

Description of the invention

The present invention relates to a medical sensor system, in particular to a continuous glucose monitoring system, comprising: a sensor implantable under the skin of a user, and an on-body module attachable to the skin in the area of the implantable sensor.

Such a system can be used to monitor certain analytes or reagents, in particular glucose or lactate, in body fluids such as blood or interstitial fluid, by reading a fully or partially implanted sensor, in particular an electrochemical sensor. Subcutaneously implanted sensors remain in the interstitial tissue for extended periods of time even up to several weeks. The measurement signal detected in vivo may then be indicative of an analyte (e.g., glucose in the blood of the subject). Monitoring may be a near real-time continuous or quasi-continuous or periodic method for frequently providing/updating analyte values without sample processing or similar user interaction.

In current practice, Continuous Glucose Monitoring (CGM) systems include a so-called body mount as a patch (patch) that includes a rigid housing portion or mounting platform to which the sensor is galvanically coupled, on which the electronics unit is mounted. Since the human body is relatively soft and flexible, the rigid housing or platform to which the sensor is attached cannot follow deflections and elongations, thereby creating shear forces that result in early detachment of the body mount from the skin. Furthermore, the platform on the body has only reduced breathability, allowing moisture to accumulate thereunder, which also undesirably reduces the possible wear time. As a further problem, open channels through the skin may cause inflammation and body infections.

WO 2010/056624a2 describes an analyte sensing device having one or more indicator electrodes adapted for prolonged use within an individual. An indicator electrode coupled to the reference electrode may be inserted into or below the dermis of the individual and may be electrically coupled to the external sensor unit.

US 2008/161656 a1 describes a device, system and method for delivering a device such as a sensor or fluid transport structure sensor combination into, for example, mammalian skin, and receiving, analyzing and displaying signals from the device such as the sensor. A system comprising: a reusable sensor assembly comprising a transmitter, a microcontroller, and a housing including a housing with an opening for receiving both a distal end of a biosensor, a sensor insertion guide structure; and transmitting means for transmitting the signal received from the sensor to the reusable sensor assembly for transmission to an external electronic monitoring unit.

US 2011/009727 a1 describes a system and method for continuous measurement of an analyte in a host. The system generally comprises: a continuous analyte sensor configured to continuously measure an analyte concentration in a host; and a sensor electronics module physically connected to the continuous analyte sensor during use of the sensor, wherein the sensor electronics module is further configured to wirelessly communicate displayable sensor information directly to a plurality of different types of display devices.

US 2017/055906 a1 describes an optical sensor, system and method for continuous glucose monitoring. In some embodiments, methods of making layered optical sensors are disclosed. The optical sensor may be formed by laminating a plurality of sheets together to form the final sensor. In some embodiments, the sensor tip comprises: an oxygen conduit, an enzyme layer, and a sensing layer. In some embodiments, the sensor comprises: a plurality of waveguides configured to guide light to and from a target material, such as an oxygen-sensing polymer. Also disclosed is a system for an adhesive system for attaching an optical sensor-emitter system. Methods and systems for a sensor inserter system are also disclosed. The inserter can include a lancet tip that includes a raised feature attached to a first surface of the lancet tip.

US 2016/051735 a1 describes a method, material, apparatus and system for electrically charged polymeric surfacing (paving) and sealing (eps). The method comprises the following steps: delivering the surfacing material to the interior surface of a blood vessel, tissue lumen, or other hollow space, delivering an electronic component to the surface, and forming a conformal device comprising the surfacing material and the integrated electronic component. The integrated electronic components may be uniformly or non-uniformly distributed in the material, such as on the top, middle, and/or bottom of the polymer material. The device is biocompatible and preferably biodegradable or bioerodible. The device integrates electrical properties useful for sensing or detecting one or more analytes, signals or conditions, transmitting or generating signals, or releasing therapeutic, prophylactic or diagnostic agents. Optionally, the device is a smart device that includes feedback and logic to respond to changes in local conditions.

EP 3138489 a1 describes a kit (kit) for determining the concentration of at least one analyte in a body fluid of a user. The kit comprises: a) a sensor module, the sensor module comprising: i. at least one sensor element adapted to determine a concentration of an analyte, wherein the sensor element is at least partially implantable in a body tissue of a user; at least one control device connected to the sensor elements, wherein the control device comprises at least one data collection device adapted to collect measurement data acquired by using the sensor elements, wherein the control device further comprises at least one wireless near field communication device adapted to transmit measurement data, wherein the sensor module comprises a sensor module mechanical interface; b) at least one data reader module adapted to receive measurement data transmitted by the sensor module via wireless near field communication, wherein the data reader module comprises at least one data storage device and is adapted to store the measurement data; c) at least one data transmission module adapted to receive the measurement data transmitted by the sensor module via wireless near-field communication, wherein the data transmission module comprises at least one wireless far-field communication device, wherein the wireless far-field communication device is adapted to transmit at least part of the measurement data to an external device via wireless far-field communication. The data reader module and the data transmission module each comprise a mechanical interface adapted to reversibly engage the sensor module mechanical interface, thereby alternatively creating a fixed spatial relationship between the sensor module and the data reader module or between the sensor module and the data transmission module.

On this basis, it is an object of the invention to further improve the known system and to provide a design that allows long-term wear and wearing comfort.

Combinations of features recited in independent claims are presented to achieve this object. Advantageous embodiments and further developments of the invention result from the dependent claims.

The invention is based on the idea of physically separating the sensor from the flat on-body module. It is therefore proposed that the on-body module has a self-adhesive flexible electronic patch comprising only a first transmitter operable to exchange data with a separate implantable sensor via a short-range wireless connection. As used herein, the term "comprising the first transmitter" refers to embodiments wherein the electronic patch comprises only the first transmitter and to embodiments wherein the electronic patch comprises additional components, in particular additional electronic components, as will be outlined below. As used herein, the term "patch" refers to at least one arbitrarily shaped fastening element configured to be attached directly to the skin of a user, i.e., without the use of additional or additional fastening elements. As used herein, the term "self-adhesive" refers to a patch comprising at least one attachment side (e.g., bottom side) adapted to attach and/or mount the patch to skin, wherein the attachment side comprises at least one adhesive and/or is coated with at least one adhesive coating. As used herein, the term "electronic patch" refers to a patch that includes at least one electronic element. As used herein, the term "flexible electronic patch" refers to the fact that the electronic patch has flexible properties such that the electronic patch can be bent and/or stretched to follow the contours of the skin. The patch may have an stretchability of at least 20% in at least two directions, preferably in all directions. As used herein, "at least 20% stretchability" refers to a patch having a length of, for example, 10 cm (centimeters) that may be stretched to a length of at least 12 cm (centimeters). The flexible patch avoids the disadvantages of a rigid platform and at the same time allows data exchange through the skin while the sensor remains sterile and does not need to be replaced with the patch. Therefore, the entire operation period can be extended and user convenience can be significantly improved.

The medical sensor system includes: an on-body module attachable to skin in the area of the implantable sensor. As used herein, the term "skin in the area attachable to the implantable sensor" refers to the electronic patch and the implantable sensor being physically separated, in particular spatially separated. In particular, the electronic patch and the implantable sensor are not physically connected. For example, the distance between the implantable sensor and the electronic patch may be in the range from 3 to 10 mm.

In an advantageous embodiment, the flexible electronic patch comprises a Flexible Printed Circuit (FPC) provided on an insulating foil substrate (e.g. on a thin polymer film) such that the patch is bendable and/or stretchable to follow the contours of the skin.

The foil with the printed circuitry thereon may be a polyimide foil carrying the structure to be electrolessly printed. Preferably, the foil is a stretchable gas permeable foil and the structure is printed with conductive ink (comprising e.g. silver and/or carbon particles).

Advantageously, the foil substrate is stretchable in at least one direction more than 20% of its original length. In an embodiment, the foil substrate may be stretchable more than 20% in at least two directions. In an embodiment, the foil substrate is stretchable more than 20% in all directions. As used herein, in embodiments, the term "more than 20%" means that a foil substrate having a length of, for example, 10 cm (centimeters) can be stretched along its length to at least 12 cm (centimeters).

Preferably, the thickness of the insulating foil substrate is in the range of 10 to 250 microns, preferably 50 to 100 microns, more preferably 60 to 90 microns, and most preferably 70 to 80 microns. Depending on the stability of the foil, a thickness in the range of 10 to 50 microns may also be feasible.

The electronic patch may include at least one deformable electronic element and/or at least one rigid or semi-rigid electronic element. For example, the electronic patch may include: at least one flexible printed circuit comprising at least one electronic element selected from the group consisting of: at least one conductive path, at least one resistor, at least one capacitor, and at least one battery, wherein the electronic component may be a deformable component. For example, the electronic patch may include rigid or semi-rigid components, such as one or more of at least one integrated circuit chip, at least one processor, at least one storage medium, at least one antenna, and at least one battery. As used herein, the term "comprising at least one deformable electronic element and/or at least one rigid or semi-rigid electronic element" refers to: the deformable electronic element and/or the rigid or semi-rigid electronic element are part of the patch and/or are integrated within or into the patch, in particular within and/or on at least one substrate of the patch and/or within at least one layer of the patch; and/or the deformable electronic component and/or the rigid or semi-rigid electronic component are embedded in the patch; and/or a deformable electronic element and/or a rigid or semi-rigid electronic element is incorporated in the patch. For example, the patch may include: an insulating foil substrate having printed thereon, in particular directly printed, deformable electronic elements and/or rigid or semi-rigid electronic elements. In particular, the deformable electronic element and/or the rigid or semi-rigid electronic element may be integrated and/or bonded and/or embedded in the patch, such that the patch itself is arranged and/or configured as an electronic unit. Thus, the deformable electronic element and/or the rigid or semi-rigid electronic element may be constituted by the patch itself, without requiring additional and/or separate elements (such as a housing or base unit or the like) adapted to store or accommodate the deformable electronic element and/or the rigid or semi-rigid electronic element.

In order to provide a flat flexible assembly, it is preferred that the flexible printed circuit comprises at least one of a conductive path, a resistor, a capacitor and a battery formed as a deformable component. It is also conceivable that even processors and other ICs, antennas for communication, and storage media are integrated into a flexible assembly, which will result in a fully flexible FPC.

Another possibility provides that the flexible electronic patch comprises at least one of an integrated circuit chip, a processor, a storage medium, an antenna and a battery as a rigid or semi-rigid component distributed such that the electronic patch as a whole remains deformable to adapt its shape to the changing contours of the skin during use.

Advantageously, the short-range wireless connection is established via a pair of antennas which are coupled by electromagnetic induction and preferably operate in the radio frequency range. Such an antenna arrangement can be easily implemented in a flat configuration on a flexible substrate.

Particular embodiments further include: the data exchange is based on the Near Field Communication (NFC) protocol. This allows a reliable wireless connection within a desired range varying from a few millimeters up to 2 centimeters. The range of near field communication may be from 3 to 10 mm. Without security problems, data transmission can even be provided in an unencrypted manner, since transmission takes place over only a small distance.

In an advantageous embodiment, the first transmitter is operable to receive measurement values from the sensor and finally transmit calibration data to the sensor. In the latter case, the measurement accuracy can be maintained even when the sensor characteristics change. It is also contemplated that if the system is factory calibrated, calibration in use may not be required.

In another advantageous configuration, the on-body module further comprises: a patch-mounted energy supply configured to supply energy to the sensor via contactless transmission. Preferably, inductive energy transfer is provided to load a capacitor on the implanted sensor. Thus, the battery need not be integrated in the sensor. This arrangement is also safer for the patient. Further, the power supply can be maintained for a long period of time.

Advantageously, the flexible electronic patch comprises a printed battery consisting of a functional material (for example, zinc manganese dioxide system) printed on a flexible substrate. Other commercially available systems are also possible.

The fully flexible battery may be arranged in a layered configuration above or below the FPC. Depending on the arrangement of the flexible battery (which may comprise a metal foil), the antenna arrangement needs to be placed such that it is not shielded by the battery. In a particular configuration, multiple antennas may be used above and below or on the sides of the printed battery.

In yet another advantageous configuration, the on-body module further comprises a second transmitter integrated with the patch and operable for wireless data exchange with an external data acquisition device positioned in the far-field region. In such an arrangement, it is preferable that the data exchange be via the bluetooth low energy communication protocol. Preferably, such a device is configured as a handheld device and operates at a distance of at most a few meters from the patch.

To implement a closed loop system, a body-mounted pump may be provided as a separate physical entity to deliver a dose of a medicament, such as insulin, to the body of a user in response to measurements made with a sensor.

In this regard, it is further advantageous that the on-body module includes at least one of a controller, a switch, and a display (particularly, a pressure sensitive display) directly attached to the flexible patch for a case that allows a user to operate the system without remote controls.

In another advantageous embodiment, the system comprises a plurality of sensors distributed in the body area and connected to the on-body module in a network. This allows for mutual control and monitoring of different influencing parameters. In such a network, data from all sensors is transferred to the on-body module, which is now the master (master) in the system. Alternatively, any other separate sensor component may be the body. All sensors may be implemented in the form of flexible patches comprising flexible electronics. Data from these sensors may be transmitted to the remote control via the subject, preferably over a Bluetooth Low Energy (BLE) connection. There, the data may be further processed to gain a deeper understanding of the patient's glycemic state.

Preferably, the plurality of sensors are adapted to measure at least one parameter selected from the group consisting of: glucose, temperature, body movement, tremor, heart rate, sweating.

In a further aspect, a method for continuous monitoring of at least one analyte in at least one body fluid is presented. The method comprises the following steps, which may be carried out in a given order, as an example. It should be noted, however, that different orders are also possible. Further, it is also possible to carry out one or more of the method steps at a time or repeatedly. Further, it is possible to carry out two or more of the method steps simultaneously or in a timely overlapping manner. The method may comprise further method steps not listed. The method comprises the following steps: at least one medical sensor system according to any one of the embodiments as described above or in detail below is used. The method comprises the following steps:

i) attaching an on-body module to the skin of a user implanted in an area of a sensor under the skin of the user using a self-adhesive flexible electronic patch, wherein the self-adhesive flexible electronic patch comprises a first emitter;

ii) exchanging data between the first transmitter of the self-adhesive flexible electronic patch and the implantable sensor via the short-range wireless connection.

With regard to embodiments and limitations of the method, reference is made to the description of the medical system above and as described in further detail below.

Summarizing and not excluding further possible embodiments, the following embodiments may be envisaged:

example 1: medical sensor system, in particular continuous glucose monitoring system, comprising a sensor implantable under the skin of a user and an on-body module attachable to the skin in the area of the implantable sensor, wherein the on-body module has a self-adhesive flexible electronic patch comprising a first transmitter operable to exchange data with the implantable sensor via a short-range wireless connection.

Example 2: the system of embodiment 1, wherein the flexible electronic patch comprises a flexible printed circuit provided on an insulating foil substrate.

Example 3: the system of embodiment 2 wherein the thickness of the insulating foil substrate is in the range of 10-250 microns, preferably 50-100 microns, more preferably 60-90 microns, and most preferably 70-80 microns.

Example 4: the system of embodiment 2 or 3, wherein the flexible printed circuit comprises at least one of a conductive path, a resistor, a capacitor, and a battery as the deformable component.

Example 5: the system of any of embodiments 1-4, wherein the flexible electronic patch comprises at least one of an integrated circuit chip, a processor, a storage medium, an antenna, and a battery as a rigid or semi-rigid component distributed such that the electronic patch remains deformable.

Example 6: the system of any of embodiments 1-5, wherein the short-range wireless connection is established via a pair of antennas that are coupled by electromagnetic induction.

Example 7: the system of any of embodiments 1-6, wherein the data exchange is based on a Near Field Communication (NFC) protocol.

Example 8: the system of any of embodiments 1-7, wherein the first transmitter is operable to receive measurements from the sensor and ultimately transmit calibration data to the sensor.

Example 9: the system of any of embodiments 1-8, wherein the on-body module further comprises: a patch-mounted energy supply configured to supply energy to the sensor via contactless transmission.

Example 10: the system of any of embodiments 1-9, wherein the flexible electronic patch comprises a printed battery comprised of functional materials printed on a flexible substrate.

Example 11: the system of any of embodiments 1-10, wherein the on-body module further comprises a second transmitter integrated with the patch and operable for wireless data exchange with an external data acquisition device located in the far-field region.

Example 12: the system of any of embodiments 1-11, further comprising a body-mounted pump to deliver a dose of a medicament, such as insulin, to the body of the user in response to measurements made with the sensor.

Example 13: the system of any of embodiments 1-12, wherein the on-body module comprises at least one of a controller, a switch, and a display directly attached to the flexible patch for allowing a user to operate the system without remote controls.

Example 14: the system according to any of embodiments 1-13, further comprising a plurality of sensors distributed in the body region and connected to the on-body module in a network.

Example 15: the system of embodiment 14, wherein the plurality of sensors are adapted to measure at least one parameter selected from the group consisting of: glucose, temperature, body movement, tremor, heart rate, sweating.

Example 16: a method for continuous monitoring of at least one analyte in at least one bodily fluid, wherein the method comprises: use of at least one medical sensor system according to any of the preceding embodiments, wherein the method comprises the steps of:

i) attaching an on-body module to the skin of a user implanted in an area of a sensor under the skin of the user using a self-adhesive flexible electronic patch, wherein the self-adhesive flexible electronic patch comprises a first emitter;

ii) exchanging data between the first transmitter of the self-adhesive flexible electronic patch and the implantable sensor via the short-range wireless connection.

The invention will be further elucidated below on the basis of an example of embodiment which is schematically shown in the drawing, in which:

FIG. 1 is a cross-sectional and partial 3D expanded view of a medical sensor system including a body-mounted flexible patch and a skin-implanted sensor interconnected by a wireless connection;

FIG. 2 is a cross-sectional view of another medical sensor assembly similar to FIG. 1 and including a patch pump worn on the body;

fig. 3 is a top view of a network of on-body modules including various skin-implanted sensors.

Referring to fig. 1, a medical sensor system 10 for continuous analyte monitoring (particularly continuous glucose monitoring) in a bodily fluid comprises: at least one on-body module 12; a completely subcutaneously implanted glucose sensor 14 disposed completely in subcutaneous tissue beneath the skin; and an optional handheld data acquisition device 16 for receiving information from module 12.

The module 12 may be attached to the skin 18 of the user in the area of the implanted sensor 14. For this purpose, the module 12 comprises: a self-adhesive planar electronic patch 20 based on a flexible foil material 22. The electronic patch 20 has: a bottom side coated with an adhesive 23 to attach the patch 20 to the skin 18 of the user; and a top side 24 facing away from the skin for carrying a flexible printed circuit and conductive paths 26; and finally a rigid or semi-rigid electronic component 27, which is mounted directly on the patch foil 22.

A first transmitter 28 mounted on the electronic patch 20 is operable to exchange data with the implantable sensor 14 via a short-range wireless connection 30. This connection may be established via the patch 20 and antennas on the sides of the sensor 14, which are coupled by electromagnetic induction. The data exchange may be based on the Near Field Communication (NFC) protocol, which is known per se to the skilled person.

In this manner, the first transmitter 28 may be operated to transmit calibration data to the sensor 14. In the other direction, sensor 14 transmits analyte readings and/or other measurement data to patch 20 for further processing in electronics assembly 27.

To avoid any galvanic connection through the skin 18, the module 12 further comprises a patch-mounted energy supply 32 configured to supply the sensor 14 with electrical energy by contactless transmission via an inductive path 34. The energy supply 32 may be implemented as a printed battery consisting of functional electrodes and electrolyte material printed on a flexible substrate.

As is also evident from fig. 1, the on-body module 12 further comprises: a second transmitter 36 integrated with the patch 20 and operable for wireless data exchange with the external data acquisition device 16. Here, a transmission path 38 may be provided for far-field communication over a range of at least several meters. In addition to receiving information from module 12, data acquisition device 16 may also allow control of module 12.

The disposable sensor 14 may include electrodes that contact interstitial fluid and provide, for example, an electrochemical reaction-based reading of the analyte. In particular, the glucose reading may be correlated to a blood glucose level for allowing a user to perform continuous or quasi-continuous in vivo monitoring.

As further illustrated in fig. 2, the system 10 may also include a body-mounted pump 40 for delivering doses of the medicament to a body 42 of the user. The pump 40 may be disposed on an adhesive patch 44 directly on the skin 18. In operation, the pump 40 receives control signals from the module 12 to supply bolus (bolus) doses of insulin in response to measurements made with the sensor 14. For improved convenience, the module 12 includes a controller 46, the controller 46 including an interface for allowing a user to operate the system 10 without remote controls.

In the embodiment of fig. 3, a plurality of sensors 14 are distributed in the body area of the user and connected to on-body module 12 in a wireless network 48. The sensors 14 are adapted to measure different body parameters, such as glucose, body temperature and movement, tremor, heart rate, perspiration. In this network 48, data from all sensors 14 (including the primary and secondary sensors assigned to the module) is transmitted to on-body module 12, which on-body module 12 operates as the master in the system. The auxiliary sensor may be implemented in the form of a flexible patch comprising flexible electronics. The acquired data may be communicated to the remote device 16 via the subject, preferably through a Bluetooth Low Energy (BLE) connection.

Claims (15)

1. A medical sensor system, in particular a continuous glucose monitoring system (10), comprising a sensor (14) implantable under the skin (18) of a user and an on-body module (12) attachable to the skin (18) in the area of the implantable sensor (14), wherein the on-body module (12) has a self-adhesive flexible electronic patch (20) comprising a first transmitter (28) operable to exchange data with the implantable sensor (14) via a short-range wireless connection (30).

2. The system according to the preceding claim, wherein the flexible electronic patch (20) comprises a flexible printed circuit (26) provided on an insulating foil substrate (22).

3. System according to the preceding claim, wherein the thickness of the insulating foil substrate (22) is in the range of 10-250 microns, preferably 50-100 microns, more preferably 60-90 microns, and most preferably 70-80 microns.

4. The system according to either of the two preceding claims, wherein the flexible printed circuit (26) comprises at least one of a conductive path, a resistor, a capacitor and a battery as deformable component.

5. The system according to any one of the preceding claims, wherein the flexible electronic patch (20) comprises at least one of an integrated circuit chip, a processor, a storage medium, an antenna and a battery as a rigid or semi-rigid component (27) distributed such that the electronic patch (20) remains deformable.

6. The system according to any of the preceding claims, wherein the short-range wireless connection (30) is established via a pair of antennas, the pair of antennas being coupled by electromagnetic induction.

7. The system of any preceding claim, wherein the data exchange is based on a Near Field Communication (NFC) protocol.

8. The system of any preceding claim, wherein the first transmitter (28) is operable to receive measurements from the sensor (14) and ultimately transmit calibration data to the sensor (14).

9. The system according to any one of the preceding claims, wherein the on-body module (12) further comprises a patch-mounted energy supply device (32) configured to supply energy to the sensor (14) by contactless transmission.

10. The system according to any one of the preceding claims, wherein the flexible electronic patch (20) comprises a printed battery consisting of functional material printed on a flexible substrate.

11. The system according to any of the preceding claims, wherein the on-body module (12) further comprises a second transmitter (36) integrated with the patch (20) and operable for wireless data exchange with an external data acquisition device (16) positioned in a far-field region.

12. The system of any preceding claim, further comprising a body-mounted pump (40) to deliver a dose of medicament, such as insulin, to a user's body (42) in response to measurements made with the sensor (14).

13. The system of any preceding claim, wherein the on-body module (12) comprises at least one of a controller (46), a switch, and a display directly attached to the flexible patch (20) for allowing a user to operate the system without remote controls.

14. The system according to any one of the preceding claims, further comprising a plurality of sensors (14) distributed in a body area and connected to the on-body module (12) in a network (48), wherein the plurality of sensors (14) are adapted to measure at least one parameter selected from the group consisting of: glucose, temperature, body movement, tremor, heart rate, sweating.

15. A method for continuous monitoring of at least one analyte in at least one bodily fluid, wherein the method comprises: use of at least one medical sensor system according to any of the preceding claims, wherein the method comprises the steps of:

i) attaching an on-body module (12) to a user's skin (18) implanted in an area of a sensor (14) under the user's skin (18) using a self-adhesive flexible electronic patch (20), wherein the self-adhesive flexible electronic patch (20) comprises a first transmitter (28);

ii) exchanging data between the first transmitter (28) of the self-adhesive flexible electronic patch (20) and the implantable sensor (14) via a short-range wireless connection (30).