# Patent

## Title
Flexible patch for fluid delivery and monitoring body analytes

## Abstract

A wearable, conductive textile patch is provided that may include any of a number of features for monitoring body analytes and/or delivering fluids to a body. In one embodiment of the invention, a single, patch-mounted system monitors glucose levels of a diabetic person and provides appropriate doses of insulin in response to the glucose measurements. A hand-held user interface can be provided for wirelessly controlling the system and/or receiving information from it. Conductive pathways can be formed in the fabric of the patch. Components that can be integrated into the flexible patch include a power source, controller, transmitter, antenna, temperature and other sensors, fluid pump, infusion set, electrical pathways, switches, controls, electrodes, connectors, resistors and other circuit elements. Such components can be embedded, interwoven or coated on to the flexible patch instead of or in addition to surface mounting. Methods associated with use of the flexible patch system are also covered.

## Background
FIELD OF THE INVENTION
The present invention relates to medical devices for monitoring analytes in a living body and delivering fluids thereto, such as monitoring glucose levels and delivering insulin to people with diabetes. More particularly, the invention relates to analyte monitoring and fluid delivery systems integrated into a flexible patch.
BACKGROUND OF THE INVENTION
In recent years, people with diabetes have typically measured their blood glucose level by lancing a finger tip or other body location to draw blood, applying the blood to a disposable test strip in a hand-held meter and allowing the meter and strip to perform an electrochemical test of the blood to determine the current glucose concentration. Such discrete, in vitro testing is typically conducted at least several times per day. Continuous in vivo glucose monitoring devices are currently being developed to replace in vitro devices. Some of these continuous systems employ a disposable, transcutaneous sensor that is inserted into the skin to measure glucose concentrations in interstitial fluid. A portion of the sensor protrudes from the skin and is coupled with a durable controller and transmitter unit that is attached to the skin with adhesive. A wireless handheld unit is used in combination with the skin-mounted transmitter and sensor to receive glucose readings periodically, such as once a minute. Every three, five or seven days, the disposable sensor is removed and replaced with a fresh sensor which is again coupled to the reusable controller and transmitter unit. With this arrangement, a person with diabetes may continuously monitor their glucose level with the handheld unit. Detailed descriptions of such a continuous glucose monitoring system and its use are provided in U.S. Pat. No. 6,175,752, issued to Abbott Diabetes Care Inc., formerly known as TheraSense, Inc., on Jan. 16, 2001, which is incorporated by reference herein in its entirety.
Portable insulin pumps are widely available and are used by diabetic people to automatically deliver insulin over extended periods of time. Currently available insulin pumps employ a common pumping technology, the syringe pump. In a syringe pump, the plunger of the syringe is advanced by a lead screw that is turned by a precision stepper motor. As the plunger advances, fluid is forced out of the syringe, through a catheter to the patient. Insulin pumps need to be very precise to deliver the relatively small volume of insulin required by a typical diabetic (about 0.1 to about 1.0 cm3 per day) in a nearly continuous manner. The delivery rate of an insulin pump can also be readily adjusted through a large range to accommodate changing insulin requirements of an individual (e.g., various basal rates and bolus doses) by adjusting the stepping rate of the motor. In addition to the renewable insulin reservoir, lead-screw and stepper motor, an insulin pump includes a battery, a controller and associated electronics, and typically a display and user controls. A typical insulin pump has a footprint about the size of a deck of cards and can be worn under clothing or attached with a belt clip. A disposable infusion set is coupled with the pump to deliver insulin to the person. The infusion set includes a cannula that is inserted through the skin, an adhesive mount to hold the cannula in place and a length of tubing to connect the cannula to the pump.
The continuous glucose monitoring and insulin delivery systems described above include various drawbacks. The rigid, flat mounting surfaces of the skin-mounted transmitters currently being developed can make them uncomfortable to wear. Additionally, since these transmitter units do not conform to the portion of the body they are mounted to, adherence to the skin and the locations on the body available for use can be limited. Currently available insulin pumps are complicated and expensive pieces of equipment costing thousands of dollars. The overall size and weight of the insulin pump and the long length of infusion set tubing can make currently available pumping systems cumbersome to use. Additionally, because of their cost, currently available insulin pumps have an intended period of use of up to two years, which necessitates routine maintenance of the device such as recharging the power supply and refilling with insulin.
Various attempts to significantly miniaturize and combine the monitoring and pumping systems described above while making them more reliable, less complex and less expensive have not been successful. Constraints which hinder such development efforts include the system requirements of sensors, insulin supplies and batteries which require periodic replacement, and the need to reduce risk of infection, increase user comfort and ease of use.
SUMMARY OF THE INVENTION
According to aspects of some embodiments of the present invention, an analyte monitoring and/or fluid delivery system is provided having components integrated into a flexible textile patch. The flexible patch may be configured to be worn on the skin of a person or animal. In one embodiment of the invention, a single, patch-mounted system monitors glucose levels of a diabetic person and may provide appropriate doses of insulin in response to the glucose measurements. According to other aspects of the invention, a hand-held user interface may be provided for wirelessly controlling the system and/or receiving information from it.
In some embodiments of the invention, conductive pathways are formed in the fabric of the patch. Components that may be integrated with the flexible patch include, but are not limited to: a power source, controller, transmitter, antenna, temperature and other sensors, fluid pump, infusion set, electrical pathways, switches, controls, electrodes, connectors, resistors and other circuit elements. Such components may be embedded, interwoven or coated on to the flexible patch instead of or in addition to surface mounting.
The flexible patch can be constructed of polyester, nylon, polyurethane, Lycra® or other synthetic or natural fibers. In one embodiment, the patch has elastomeric properties that come from properties of the fibers themselves, or from how the fibers are combined to form patch. The flexible patch may be woven, non-woven, knitted, spun or constructed of a textured film, preferably to form an electro-active fabric. Conductive aspects of the textile may come from fine metal wires, either in the yarn used to make the fabric of the patch or woven into the fabric alongside ordinary textile fibers. Alternatively, the electrical properties of patch 12 may come from inherently conductive polymers or nanocomposites deposited as coatings on the fabric's fibers.
According to aspects of some embodiments of the invention, the flexible patch may be soft, stretchable and breathable to increase patient comfort during use. The fabric of the flexible patch may be rolled, crumpled and folded without damaging its functionality. The flexible patch may also be constructed or coated to be flame resistant, water-resistant, or waterproof.
According to aspects of some embodiments of the invention, portions of a flexible patch system or the entire system itself may be disposable, for instance after a predetermined period of use and/or after a particular consumable, such as an insulin supply, is exhausted. For example, just an analyte sensor, an infusion set and a mounting adhesive may be disposable, while the rest of the flexible patch system is reusable. In such an arrangement, an insulin or other fluid reservoir may be refillable, and/or may comprise a removable cartridge. A portion of electronic circuitry and/or fluid pump may also be removed and reused with a new flexible patch while the remainder of the used patch is discarded. Alternatively, a flexible patch monitoring and fluid delivery system may be constructed inexpensively enough, according to aspects of the present invention, so that the entire system can be disposed of and replaced periodically. Such arrangements would have the advantage of lowering the fixed and recurring costs associated with the use of a monitoring and/or fluid delivery system.
Various analytes may be monitored using aspects of the present invention. These analytes may include, but are not limited to, lactate, acetyl choline, amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase (e.g., CK-MB), creatine, DNA, fructosamine, glucose, glutamine, growth hormones, hematocrit, hemoglobin (e.g. HbA1c), hormones, ketones, lactate, oxygen, peroxide, prostate-specific antigen, prothrombin, RNA, thyroid stimulating hormone, and troponin, in samples of body fluid. Monitoring systems may also be configured to determine the concentration of drugs, such as, for example, antibiotics (e.g., gentamicin, vancomycin, and the like), digitoxin, digoxin, drugs of abuse, theophylline, warfarin and the like. Such analytes may be monitored in blood, interstitial fluid and other bodily fluids. Fluids that can be delivered include, but are not limited to, insulin and other medicines.



BRIEF DESCRIPTION OF THE DRAWINGS
Each of the figures diagrammatically illustrates aspects of the invention. Of these:
FIG. 1 is a plan view showing an exemplary embodiment of a flexible patch system constructed according to aspects of the present invention;
FIG. 2 is a side view of the system of FIG. 1 shown mounted on a patient P;
FIG. 3 is a perspective view illustrating the use of the system of FIG. 1 on a person.



Variation of the invention from that shown in the figures is contemplated.
DETAILED DESCRIPTION
The following description focuses on one variation of the present invention. The variation of the invention is to be taken as a non-limiting example. It is to be understood that the invention is not limited to particular variation(s) set forth and may, of course, vary. Changes may be made to the invention described and equivalents may be substituted (both presently known and future-developed) without departing from the true spirit and scope of the invention. In addition, modifications may be made to adapt a particular situation, material, composition of matter, process, process act(s) or step(s) to the objective(s), spirit or scope of the present invention.
FIG. 1 shows a top view of an exemplary embodiment of a combined fluid delivery and analyte monitoring system 10 constricted according to some aspects of the present invention, while FIG. 2 shows an elevational end view of system 10 mounted on the skin of patient P. Flexible fabric patch 12 forms the base of system 10. Flexible patch 12 may be provided with an adhesive on a bottom surface to secure patch 12 to the skin of the patient during use. Various components may be attached to or integrated into flexible patch 12, such as power source 14, controller and transmitter module 16, antenna 18, temperature sensor 20, fluid pump 22 and infusion set 24. Electrical pathways 26 may be integrated into flexible patch 12 for interconnecting components of system 10.
Flexible patch 12 may be provided with a thicker area 28, generally towards its center, to afford sufficient support for mounting components. In one embodiment, central area 28 is about 1 mm thick. A peripheral area 30 of flexible patch 12 may be made thinner to promote attachment and adhesion to the skin, particularly as the skin moves and flexes.
Power source 14 may be one or more solar cells, disposable or rechargeable batteries or device, an electrochemical device generating power from an analyte of the patient, and/or other power source suitable for satisfying the power requirements of the components located on flexible patch 12. Such power sources may be directly integrated into flexible patch 12, or removably inserted into a holder attached to patch 12. Power source 14 may itself be flexible by constructing a battery from one or more layers of paper or fabric. Such a paper or fabric battery can convert chemical energy directly into electricity by oxidizing metal on one side of the layer and allowing an oxide to be reduced on the other side when the battery is connected. The metal may be zinc, aluminum, nickel or other metals, the oxide can be manganese oxide, or other oxides, and the paper or fabric layer can contain an electrolyte. Such flexible batteries are currently being developed by companies such as Enfucell Ltd. of Espoo, Finland (www.enfucell.com). Flexible patch 12 itself may comprise one or more layers that can be used to form a flexible battery. Such an arrangement can reduce the need for electrical connectors for the battery, thereby contributing to making the overall system 10 smaller, softer, more conforming to the user and more comfortable to wear.
Circuitry for controller and transmitter 16 may be directly integrated into flexible patch 12. Alternatively, controller and transmitter 16 can be constructed using traditional electronic component assembly techniques then physically and electronically attached to patch 12. Such attachment of module 16 can be permanent or removable. Permanent attachment can be achieved by soldering electrical leads of module 16 to electrical leads on patch 12. Removable attachment of module 16 can be achieved with a traditional electrical connector or with a snap type fitting 32 having electrical pathways interconnecting module 16 to patch 12. Module 16 is preferably powered by power source 14, but may include its own power source in addition to or instead of power source 14.
Antenna 18 preferably is at least somewhat flexible to provide enhanced fit and comfort of patch 12. Antenna 18 can be a separate element physically and electrically coupled with patch 12, but preferably is formed by a conductive layer or layers of patch 12. Antenna 18 is electrically connected to controller and transmitter module 16 to transmit radio frequency (RF) signals such as analyte readings therefrom to an external device, such as a handheld user interface. If module 16 is configured to receive information as well, antenna 18 can be arranged to both transmit and receive RF signals. An infrared (IR) transmitter or transceiver (not shown) can be utilized in addition to or instead of antenna 18 to wirelessly communicate information between system 10 and an external device. A transducer coil and/or cable connector (not shown) can also be provided for external communications, such as to a computer for running diagnostics, or uploading or downloading information.
Flexible patch 12 may be provided with one or more sensor sites 34 for receiving transcutaneous analyte sensors. Multiple sensors can be used simultaneously to provide redundant analyte readings. Alternatively, one sensor may be inserted at a time. After each sensor is used for a predetermined period, such as three, five or seven days each, it can be removed and a fresh sensor can be inserted at an unused sensor site. Preferably, once all of the sensor sites 34 of a particular patch 12 have been used, patch 12 is removed from the skin and a new patch 12 is applied to a different location on the user's skin. Alternatively, a portion of patch 12 can be reused with a new adhesive portion.
Transcutaneous analyte sensors can be inserted into the user's skin using an automatic introducer or inserter device, such as those described in U.S. patent application Ser. No. 10/703,214, published Jul. 8, 2004 under publication number 20040133164, now U.S. Pat. No. 7,381,184, incorporated herein by reference in its entirety. An inserted sensor can be electrically connected to controller and transmitter module 16 directly, with external conductors or through internal electrical pathways within flexible patch 12. The sensors may include adhesive mounts, or some type of mounting feature such as one or more snaps, hooks, clamps, pins, clips or other means molded onto or attached to the patch to secure the sensor to flexible patch 12 or to the user's skin during use.
Monitoring and delivery system 10 can also include a temperature sensor 20 for sensing ambient temperature, skin surface temperature or sub-dermal temperature. Ideally, sub-dermal temperature is measured to more accurately calibrate the readings taken by the analyte sensors, since such readings are typically temperature sensitive. However, sub-dermal temperature measurement can be impractical, since this typically necessitates another puncture to the user's skin. Placing a temperature sensor below the surface of the skin can cause discomfort and increased chance of infection. Accordingly, temperature sensor 20 can be mounted to or integrated with the bottom surface of flexible patch 12 to measure the local surface temperature of the skin. From this temperature reading, the higher sub-dermal temperature may be estimated for the depth of penetration associated with sensor 20. In one embodiment, temperature sensor 20 may be connected to controller and transmitter module 16 with internal electrical pathways within flexible patch 12.
A fluid pump 22, such as for delivering insulin or other medicine, can also be located on flexible patch 12. In this exemplary embodiment, fluid pump 22 includes a removable fluid reservoir 36. Reservoir 36 may be a disposable or refillable vial that is replaced by another vial when depleted. Reservoir 36 may be flexible so that it collapses like a balloon when its contents are emptied, or it may include a flexible diaphragm portion. Alternatively, reservoir 36 may be a rigid cylinder with a plunger 38 that forces fluid out when advanced into the reservoir 36. Actuator 40 may be a stepper motor, a shape-memory alloy actuator or other suitable mechanism for advancing plunger 38 or otherwise moving fluid out of reservoir 36. A shape-memory alloy actuator is preferred because of its small size, simplicity and reliability. It's low cost of manufacture also allows pump 22 to be disposable with patch 22 if desired. Details of such a shape-memory alloy driven pump are provided in U.S. patent application Ser. No. 10/683,659, published Jun. 17, 2004 under Publication No. 20040115067A1, now U.S. Pat. No. 6,916,159, incorporated herein by reference in its entirety. Reservoir 36 need not be removable from pump 22 and/or patch 12, particularly if patch 12 is designed to be disposed of after the fluid is depleted.
Pump 22 preferably is powered by power source 14, but may have its own power source. Internal conductive pathways 26 can be used to connect pump 22 with power source 14 and/or controller and transmitter module 16. Pump 22 may be removably or fixedly attached to patch 12. Pump 22 or a pump mounting base may be attached to patch 12 by sandwiching a portion of the patch material between the pump or base and a plate or washer(s) on the opposite side. Alternatively, pump 22 or a mounting base may be attached to patch 12 with an adhesive, fasteners or other suitable means.
In operation, pump 22 can receive control signals from controller and transmitter module 16, causing actuator 40 to push fluid from reservoir 36 into tubing 42 of infusion set 24, through cannula 44 and into the patient. Infusion set 24 may include an adhesive mount 46 for securing the distal end of infusion set 24 to patch 12 or directly to the patient's skin. The proximal end of infusion set 24 may be removably connected to an output port 48 of pump 22. Multiple sites 50 may be provided in the thin region 30 of patch 12 for alternately placing infusion sets 24. An automatic inserter or introducer may be used to insert cannula 44 of infusion set 24 into the patient. Preferably, a single puncture device can be used to insert cannulas 44 and the transcutaneous analyte sensors described above. After a predetermined period of use, typically 3 days, infusion set 24 can be removed by lifting adhesive mount 46, removing cannula 44 from the patient and disconnecting tubing 42 from pump output port 48. A fresh infusion set 24 may then be placed in another one of the sites 50 and connected to pump 22. It may be advantageous to separate infusion set insertion sites 50 as far as possible from sensor insertion sites 34 as shown so that the local effect of the infusion of insulin or other fluid does not interfere with glucose monitoring or other analyte measurement. In one embodiment, infusion sites 50 are spaced about 1 inch apart.
In arranging system 10 components on flexible patch 12, the longitudinal axis of components such as controller and transmitter module 16, antenna 18 and pump 22 may be aligned with each other. This allows the overall system to be highly flexible in at least one direction. Since these components may be fairly long and rigid, the exemplary system 10 shown in FIG. 1 is more flexible along the y-axis shown than along the x-axis. With such an arrangement, patch 12 can more compliantly conform to curves of a patient's body when the y-axis is aligned with the direction of the sharpest curve at the application site of patch 12. An example of such an alignment is shown in FIG. 3, where patch 12 is attached to an upper arm of a patient P. As shown, the more compliant y-axis of flexible patch 12 is arranged horizontally to traverse the curve of the arm, while the less compliant x-axis is arranged vertically along the straighter, longitudinal axis of the arm. System 10 may be adhered to other suitable locations of the body, such as the torso, thigh or calf. In this exemplary embodiment, system 10 is about 4 inches long along the x-axis, about 3 inches long along the y-axis and has a maximum thickness of about 0.75 inches at pump 22.
Flexible patch 12 itself can be constructed of polyester, nylon, polyurethane, Lycra® or other synthetic or natural fibers. Preferably, patch 12 has elastomeric properties that come from properties of the fibers themselves, or from how the fibers are combined to form patch 12. Patch 12 can be woven, non-woven, knitted, spun or constructed of a textured film, preferably to form an electro-active fabric. Conductive aspects of the textile can come from fine metal wires, either in the yarn used to make the fabric of patch 12 or woven into the fabric alongside ordinary textile fibers. Alternatively, the electrical properties of patch 12 can come from inherently conductive polymers or nanocomposites deposited as coatings on the fabric's fibers.
As discussed above, various components of system 10 can be woven directly into the fabric of patch 12, including, but not limited to, complex electronic pathways, circuits, controls, electrodes, temperature and other sensors, traces, connectors, resistors, antenna, batteries, switches and other components. Switches and other controls can be incorporated into flexible patch 12 by using a multilayered fabric. For example, three electro-active layers can be used. Two outer conductive layers can surround an inner resistive layer that separates the conductive layers until the layers are momentarily pressed together.
Using fabrics as discussed above, flexible patch 12 can be soft, stretchable and breathable to provide patient comfort during use. Existing fabrics can provide a high moisture vapor transmission rate (MVTR). Such fabrics can be rolled, crumpled and folded without damaging functionality. Patch 12 may also be constricted or coated to be flame resistant, waterproof or water-resistant if desired.
Further information on suitable fabrics, general construction and component integration methods for flexible patch 12 may be obtained from companies currently developing “smart fabrics” or conductive textiles, such as Textronics (www.textronics.com), Konarka (www.konarka.com), Nanosonic (www.nanosonic.com), Eleksen (www.eleksen.com) and Eeonyx (www.eeonyx.com). For instance, Eeonyx has a proprietary process for coating textiles with inherently conductive polymers based on doped polypyrrole. The company polymerizes the materials in situ—or on the surface of the fabric itself—so the coating material fills interstices in the surface and forms a physical bond with the fibers. See also “Fabrics Get Smart”, by Joseph Ogando, Design News, May 15, 2006 (www.designmews.com/article/ca6330247.html), incorporated herein by reference in its entirety.
As for additional details pertinent to the present invention, materials and manufacturing techniques may be employed as within the level of those with skill in the relevant art. The same may hold true with respect to method-based aspects of the invention in terms of additional acts commonly or logically employed. Also, it is contemplated that any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein. Likewise, reference to a singular item, includes the possibility that there are plural of the same items present. More specifically, as used herein and in the appended claims, the singular forms “a,” “and,” “said,” and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The breadth of the present invention is not to be limited by the subject specification, but rather only by the plain meaning of the claim terms employed.

## Claims

1. A method for measuring analyte utilizing a body analyte monitoring system, the body analyte monitoring system having a flexible patch, a first analyte sensor, a second analyte sensor, a power source, and a controller, wherein a plurality of sensor insertion sites are on the flexible patch, and wherein the flexible patch is configured to be worn on a skin surface and to receive one or more analyte sensors at one or more of the plurality of sensor insertion sites, the method comprising:
inserting the first analyte sensor into one of the plurality of predefined sensor insertion sites through the skin surface and in contact with fluid under the skin surface at the one of the plurality of predefined sensor insertion sites;
removing the first analyte sensor from the one of the plurality of predefined sensor insertion sites after the lifetime of the first analyte sensor has expired while the flexible patch is retained on the skin surface;
inserting the second analyte sensor in another one of the plurality of predefined sensor insertion sites through the skin surface and in contact with the fluid under the skin surface at the another one of the plurality of predefined sensor insertion sites after the first analyte sensor is removed from the one of the predefined sensor insertion sites and while the flexible patch is retained on the skin surface; and
communicating signals from the second analyte sensor to the controller, wherein the controller is powered by the power source.

2. The method of claim 1, further comprising transmitting data from the second analyte sensor to a second device using a transmitter integrated with the flexible patch, wherein the transmitter is powered by the power source controlled by the controller.

3. The method of claim 2, further comprising transmitting the data using a flexible antenna integrated with the flexible patch.

4. The method of claim 1, further comprising transmitting data corresponding the monitored analyte level and receiving information from a second device using a transceiver integrated with the flexible patch.

5. The method of claim 4, further comprising transmitting signals from the transceiver and receiving signals from the second device using an antenna integrated with the flexible patch.

6. The method of claim 1, wherein the second analyte sensor generates signals corresponding the monitored analyte level in the fluid under the skin surface.

7. The method of claim 5, wherein the controller, the transceiver, and the antenna are located along a longitudinal axis of the flexible patch.

8. The method of claim 1, wherein the flexible patch includes a material with elastomeric properties.

9. The method of claim 5, wherein at least one of the first or the second analyte sensors, the power source, the controller, the transceiver, and the antenna are woven into the flexible patch.

10. The method of claim 1, wherein one or more of the first and second analyte sensors includes a plurality of electrodes, wherein the plurality of electrodes include a working electrode comprising an analyte-responsive enzyme chemically bonded to a polymer disposed on the working electrode.

11. The method of claim 10, wherein the analyte-responsive enzyme is crosslinked with the polymer.

12. The method of claim 10, wherein the working electrode comprises a mediator.

13. The method of claim 12, wherein the mediator is chemically bonded to the polymer disposed on the working electrode.

14. The method of claim 1, wherein one or more of the first and second analyte sensors includes a plurality of electrodes, wherein the plurality of electrodes include a working electrode comprising a mediator chemically bonded to a polymer.

15. The method of claim 14, wherein the mediator is crosslinked with the polymer disposed on the working electrode.

16. The method of claim 1, wherein the power source associated with the flexible patch is flexible.

17. The method of claim 16, wherein the power source includes a flexible battery directly integrated with the flexible patch.

18. The method of claim 1, wherein the flexible patch is removed from the skin surface after the second analyte sensor is removed from the another one of the plurality of predefined sensor insertion sites.