Dermal electrode on electrochemical biosensor

Abstract

A device includes a monitor. The monitor includes at least one sensor configured to sense an electrical signal indicative of an analyte level of an analyte of a patient. The sensor includes a first electrode and a second electrode. The first electrode and the second electrode form an electrode pair configured to interact with the analyte and generate the electrical signal in response to the interaction. The second electrode is configured to be positioned on an epidermal layer of the patient.

Description

Docket No. : A0010697WO01 / 1277- 125 WOO 1 DERMAL ELECTRODE ON ELECTROCHEMICAL BIOSENSOR

[0001] This application claims the benefit of U.S. Provisional Patent Application No.63 / 719,400, filed 12 November 2024, the entire contents of which is incorporated herein by reference.TECHNICAL FIELD

[0002] This disclosure relates to biosensors.BACKGROUND

[0003] Biosensors are configured to detect and / or quantify the amount of an analyte in a patient's body, which enables patients and medical personnel to monitor physiological conditions within the patient's body. In some examples, in a patient with diabetes, it may be beneficial to monitor levels of one or more analytes on a continuing basis (e.g., glucose). Thus, glucose sensors have been developed for use in obtaining an indication of glucose levels in a diabetic patient. Such indications are useful in monitoring and / or adjusting a treatment regimen, which typically includes administration of insulin to the patient.

[0004] A patient can measure their analyte levels using a measurement device such as a test strip meter. In some examples, an analyte level in a patient may be monitored continuously. For example, a continuous glucose measurement system (or a continuous glucose monitor (CGM)) may be configured to monitor interstitial glucose. Some example continuous analyte monitoring systems include subcutaneous (or short-term) sensors and implantable (or long-term) sensors.SUMMARY

[0005] In general, this disclosure describes devices and techniques for determining an analyte level in a patient using a monitor that includes a sensor that includes an electrode pair. The electrode pair includes a first electrode, called a working electrode, and a second electrode, called a counter electrode. At least one of first electrode and the second electrode (e.g., the electrode pair) interact with the analyte to generate or generate a change in an electrical signal indicative of an analyte level of the analyte of the patient. The working electrode is typically inserted into the targeted tissue (e.g., an interstitial fluid layer, a vein, or the like) by positioning the working electrode on a sensor flex and inserting the sensor flex into the patient’s body. The counter electrode is often also included on the sensor flex.

[0006] The sensor including the working electrode and a counter electrode may be part of a monitor that continuously or intermittently senses the level (e.g., concentration in interstitialDocket No. : A0010697WO01 / 1277- 125 WOO 1 fluid) of an analyte. For example, the monitor may be a glucose monitor which regularly measures the concentration of glucose in a patient and is worn by the patient for an extended period of time (e.g., hours or days) without being removed. Reducing the size of the monitor, especially those components of the monitor which are inserted into the patient’s body, may advantageously improve wearability of the monitor and / or improve patient comfort. Furthermore, it may be desirable to sense the level of more than one analyte. For example, in the example of a glucose monitor, it may be desirable to measure the levels of one or more analytes in addition to glucose, because information about the level of these additional relevant analytes may be used by the patient, clinician, or medical devices to selectively tailor treatment of the patient (e.g., used to adjust target levels, injections of insulin, or the like).

[0007] According to devices and techniques of the present disclosure, the second electrode is configured to be positioned on an epidermal layer of the patient. Put differently, the counter electrode is worn by the patient on the skin, in devices of the present disclosure, rather than being positioned on a sensor flex and inserted into the patient. Although primarily described as an electrode pair including a first electrode, or working electrode, and a second electrode, or counter electrode, in some examples, the sensor may include a third electrode, or reference electrode. In other words, the sensor may be a two-wire system or a three-wire system.

[0008] Devices according to the present disclosure, which position the counter electrode externally (e.g., on an epidermal layer of the patient’s skin), may have several advantages over devices configured to position the counter electrode under the skin of the patient, such as on a sensor flex. For example, where the monitor is configured to sense a level of only a single analyte, positioning the counter electrode on an epidermal layer of the patient rather than on the sensor flex may allow for reducing the size (e.g., diameter and / or length) of the sensor flex, which may allow for increased patient comfort while wearing the monitor and / or increased ease of maintenance and treatment of the monitor site.

[0009] Additionally, or alternatively, positioning the counter electrode on an epidermal layer of the patient may allow for increased space on the sensor flex, which may be used to position one or more additional working electrodes as part of one or more additional sensors. The additional sensor or sensors may be configured to sense the same or a different analyte. Since the counter electrode typically has a larger surface area than the working electrode, positioning the counter electrode off of the sensor flex and on an epidermal layer of the patient may allow for the inclusion of more than one sensor in the monitor.

[0010] For instance, a second working electrode that is part of a second sensor configured to sense a second analyte may be included on the sensor flex, and a third working electrode that is part of a third sensor configured to sense a third analyte may be included on the sensor flex. TheDocket No. : A0010697WO01 / 1277- 125 WOO 1 epidermally-positioned counter electrode may be a common counter electrode, e.g., a single counter electrode that is part of each of the individual sensors of the multi-analyte monitor. In this way, devices of the present disclosure may allow for monitoring of multiple analytes using a single monitor, which may have a single counter electrode and a single sensor flex. The sensor flex may not need to be expanded in size relative to a single analyte sensor that includes a subcutaneous counter electrode to accommodate monitoring of the additional analytes because the counter electrode is positioned off of the sensor flex. As such, devices and techniques according to the present disclosure may allow for a more complete monitoring of physiological conditions of the patient by tracking the levels of more than one analyte, without adding to the size of the sensor flex, and without adding additional monitors and the associated treatment sites to the monitoring system.

[0011] In one example, a device includes a monitor. The monitor includes at least one sensor configured to sense an electrical signal indicative of an analyte level of an analyte of a patient. The sensor includes a first electrode and a second electrode. The first electrode and the second electrode form an electrode pair configured to interact with the analyte and generate a change in the electrical signal in response to the reaction. The second electrode is configured to be positioned on an epidermal layer of the patient.

[0012] In one example, a technique includes interacting an electrode pair which includes a first electrode and a second electrode with an analyte of a patient. The electrode pair is part of a sensor, and the sensor is part of a monitor. The second electrode is positioned on an epidermal layer of the patient. The technique includes generating a change in an electrical signal indicative of an analyte level of the analyte between the first electrode and the second electrode in response to the interaction with the analyte. The technique further includes outputting, from the sensor, the electrical signal indicative of the analyte level of the analyte of the patient.

[0013] In one example, a non-transitory computer-readable storage medium has stored thereon instructions that, when executed, configure a processor. The processor is configured to cause an electrode pair which includes a first electrode and a second electrode to interact with an analyte of a patient. The electrode pair is part of a sensor, and the sensor is part of a monitor. The second electrode is positioned on an epidermal layer of the patient. The processor is further configured to cause generation of an electrical signal indicative of an analyte level of the analyte between the first electrode and the second electrode in response to the interaction with the analyte. The processor is further configured to cause the sensor to output the electrical signal indicative of the analyte level of the analyte of the patient.Docket No. : A0010697WO01 / 1277- 125 WOO 1

[0014] The details of one or more examples are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims.BRIEF DESCRIPTION OF DRAWINGS

[0015] FIG. 1 is a schematic diagram illustrating an example glucose level management system, in accordance with one or more examples described in this disclosure.

[0016] FIG. 2 is a schematic diagram illustrating an example medical device including a monitor which includes a sensor.

[0017] FIG. 3 is a schematic diagram illustrating medical device including a monitor which includes a sensor which has a counter electrode configured to be positioned on an epidermal layer of the patient, in accordance with one or more examples of the present disclosure.

[0018] FIG. 4 is a schematic diagram illustrating medical device including a multi-analyte monitor which includes a sensor which has a counter electrode configured to be positioned on an epidermal layer of the patient, in accordance with one or more examples of the present disclosure.

[0019] FIG. 5 is a schematic diagram illustrating another medical device including a multianalyte monitor which includes a sensor which has a counter electrode configured to positioned on an epidermal layer of the patient, in accordance with one or more examples of the present disclosure.

[0020] FIG. 6 is a side view of an example medical device including a glucose monitor and insulin cannula, in accordance with one or more examples of the present disclosure.

[0021] FIG. 7 is a block diagram illustrating an example monitor, in accordance with one or more examples described in this disclosure.

[0022] FIG. 8 is a schematic diagram illustrating example sensors, and a voltage being applied to the sensors, in accordance with one or more examples of the present disclosure electrodes.

[0023] FIG. 9 is a graph illustrating an example electrical signal generated by a sensor which include an internal counter electrode, and an electrical signal generated by a sensor which includes an external counter electrode.

[0024] FIG. 10 is a graph illustrating example electrical signals generated by glucose sensors which include an internal counter electrode, and an electrical signal generated by a glucose sensor which includes an external counter electrode in response to a dosage of glucose solution.

[0025] FIG. 11 is a graph illustrating an example electrical signal generated by an example glucose sensor with a counter electrode located in same media as working electrode.Docket No. : A0010697WO01 / 1277- 125 WOO 1

[0026] FIG. 12 is a graph illustrating an example electrical signal generated by the example glucose sensor of FIG. 11 with additional resistance at the counter electrode which mimics the resistance of human skin.

[0027] FIG. 13 is a flowchart illustrating an example technique for determining an analyte level in a patient.DETAILED DESCRIPTION

[0028] In general, this disclosure describes devices and techniques for determining an analyte level in a patient using a monitor that includes a sensor that includes an electrode pair. The electrode pair includes a first electrode, called a working electrode, and a second electrode, called a counter electrode. At least one of the first electrode or the second electrode (e.g., the electrode pair) interact with the analyte and generate or modify an electrical signal indicative of an analyte level of the analyte of the patient. The working electrode is typically inserted into the targeted tissue (e.g., an interstitial fluid layer, a vein, or the like) by positioning the working electrode on a sensor flex and inserting the sensor flex into the patient’s body. In many different types of monitors, the counter electrode is often also included on the sensor flex.

[0029] The sensor including the working electrode and a counter electrode may be part of a monitor that continuously or intermittently senses the level (e.g., concentration in interstitial fluid) of an analyte. For example, the monitor may be a glucose monitor which regularly measures the concentration of glucose in a patient and is worn by the patient for an extended period of time (e.g., hours or days) without being removed. Reducing the size of the monitor, especially those components of the monitor which are inserted into the patient’s body, may advantageously improve wearability of the monitor and / or improve patient comfort. Furthermore, it may be desirable to sense the level of more than one analyte. In the example of a glucose monitor worn by a diabetic patient, it may be desirable to measure the levels of one or more analytes relevant to treatment of diabetes in addition to glucose, because information related to the level of these additional analytes may be used by the patient, clinician, or medical devices to selectively tailor treatment of the disease.

[0030] Patients who wear a device which includes a monitor, such as a CGM, generally do not want the monitor to interfere with their day-to-day activities. Since larger and heavier devices may be relatively more cumbersome and / or may be relatively more uncomfortable than smaller devices, it may be desirable to reduce the device in size and / or weight where possible.Furthermore, portions of the device configured to be worn under the skin may more directly impact patient comfort, so reducing the size of these components may be particularly desirable.Docket No. : A0010697WO01 / 1277- 125 WOO 1

[0031] In treatment of diabetes or other diseases, or in other situations such as athletic training, it may be desirable measure the levels of more than one analyte in a patient. For example, a diabetic patient may monitor their glucose level using a continuous glucose monitor (CGM) as part of a treatment regimen. In some examples, in addition to monitoring their glucose level, it may be beneficial to monitor one or more additional analytes, e.g., a second analyte, a third analyte, a fourth analyte, and so on. In the diabetes example, other analytes of interest may include one or more of at least one of glucose, insulin, creatinine, ketones, lactate, alcohol, sodium, potassium, hydrogen ions, hydroxide ions, oxygen, and / or chloride. Monitoring the level of more than one analyte in a patient may present a more complete picture of the patient’s status and allow for better treatment strategies with the additional data. However, interest in capturing information related to the levels of additional analytes may need to be balanced against other considerations, such as the desire for smaller monitors and / or fewer treatment sites.

[0032] The ability to add additional sensors configured to sense the level of additional analytes may be limited in other ways. For example, a monitor such as a CGM may include a sensor that is configured to sense an analyte level present within an interstitial fluid layer of the patient. The interstitial fluid layer may be below the top layers of a patient’s skin but above adjacent layers of tissue. The monitor may include a working electrode positioned on a sensor flex. The sensor flex may need to extend through the epidermis and position the working electrode in the interstitial fluid layer of the patient. The sensor flex may be limited in length such that the sensor flex must terminate before penetrating tissue underlying the interstitial fluid layer. In this way, it may be difficult to add an additional sensor configured to sense an additional analyte to the monitor, because additional length may not be added to the sensor flex.

[0033] Devices and techniques of the present disclosure may address one or more of the above-described desires and challenges of analyte monitoring. In accordance with some examples of the present disclosure, a device may include a monitor that includes a sensor that includes an electrode pair. The electrode pair includes a first electrode, called a working electrode, and a second electrode, called a counter electrode. At least one of the electrodes of the electrode pair is configured interact with the analyte and generate an electrical signal indicative of an analyte level of the analyte of the patient in response to the interaction. According to devices and techniques of the present disclosure, the second electrode is configured to be positioned on an epidermal layer of the patient. Put differently, the counter electrode is worn by the patient on the skin, rather than being located on a sensor flex and worn subcutaneously.

[0034] In some examples, the interaction between the working electrode and the analyte may be a chemical reaction that generates the electrical signal. However, the working electrode need not necessarily chemically react with the analyte generate the electrical signal. For example, theDocket No. : A0010697WO01 / 1277- 125 WOO 1 working electrode may be an ion selective electrode. In such examples, the working electrode may be covered by a membrane that only a particular ion may pass through to contact the working electrode. When the particular ion passes through the membrane and contacts the working electrode, a change may be generated in an electrical signal between the working electrode and the counter electrode. The change in the electrical signal may indicate a presence and concentration of the particular ion.

[0035] Devices according to the present disclosure, which position the counter electrode externally (e.g., on an epidermal layer of the patient’s skin), may have several advantages over devices configured to position the counter electrode under the skin of the patient. For example, where the device is configured to sense a level of only a single analyte, positioning the counter electrode on an epidermal layer of the patient rather than on the sensor flex may allow for reducing the size (e.g., diameter and / or length) of the sensor flex, which may allow for increased patient comfort while wearing the monitor and / or increased ease of maintenance and treatment of the monitor site. Devices disclosed herein may enable an increase in the surface area of a single working electrode on a sensor flex on the same size by positioning the counter electrode externally, which may enable improved performance of the working electrode.

[0036] Additionally, or alternatively, positioning the counter electrode on the epidermal layer of the patient may allow for increased space on the sensor flex, which may be used to position one or more additional working electrodes as part of one or more additional sensors. The additional sensor or sensors may be configured to sense the same or a different analyte. In this way, aspects of the present disclosure may enable multi-analyte monitoring where previously only single analyte monitoring could be accomplished.

[0037] Since the counter electrode typically has a larger surface area than the working electrode, positioning the counter electrode off of the sensor flex and on the epidermal layer of the patient may allow for the addition of more than one sensor to the monitor. For instance, a second working electrode that is part of a second sensor configured to sense a second analyte and / or a third working electrode that is part of a third sensor configured to sense a third analyte may be included on the sensor flex.

[0038] In these examples, the epidermally-positioned counter electrode may be a common counter electrode, e.g., a single counter electrode that is part of each of the individual sensors of the multi-analyte monitor. In this way, devices of the present disclosure may allow for monitoring of multiple analytes using a single monitor, which may have a single counter electrode, a single sensor flex, and multiple working electrodes. The sensor flex may not need to be expanded in size relative to a single analyte sensor that includes a counter electrode positioned on the sensor flex. In some examples, the epidermally-positioned counter electrode may beDocket No. : A0010697WO01 / 1277- 125 WOO 1 subdivided into more than one counter electrode (e.g., a first counter electrode, a second counter electrode, and a third counter electrode). In some examples, each of a plurality of working electrodes may correspond to a respective epidermally-positioned counter electrode.

[0039] As such, devices and techniques according to the present disclosure may allow for a more complete monitoring of patient physiological conditions by tracking the levels of more than one analyte, without adding to the size of the sensor flex, and without adding additional monitors and the associated treatment sites to the system. Each additional working electrode that can be added to the sensor flex may have further utility, since each additional working electrode may be part of an additional sensor that can monitor an additional analyte, and information about each additional analyte may be used to further tailor treatment. For example, a three-analyte monitor may be desirable relative to a two-analyte monitor, and a four-analyte monitor may be desirable relative to a three-analyte monitor.

[0040] Still further advantages may be realized in devices which include counter electrode positioned on an epidermal layer of the patient. For example, the transcutaneous portion of devices according to the present disclosure may be easier and / or cheaper to manufacture than devices which position the counter electrode on the sensor flex. In some examples, the transcutaneous portions of such devices may be manufactured in higher numbers on a single wafer, which may reduce the waste of materials in assembly.

[0041] In some examples, devices according to the present disclosure may position the working electrode on a sensor flex. The sensor flex may extend transcutaneous from a first end at an external surface of the patient’s skin to a second end within interstitial fluid of the patient. The working electrode (or working electrodes where the monitor is a multi-analyte monitor) may be positioned near the second end of the sensor flex in the interstitial fluid layer of the patient. The sensor may be a two-wire sensor that includes only a working electrode and a counter electrode, or the sensor may be a three-wire sensor that includes a working electrode, a counter electrode, and a reference electrode. In examples where the sensor is a three-wire sensor, the reference electrode may be positioned on the sensor flex.

[0042] The counter electrode may be the largest electrode by surface area of the sensor. For example, for efficiency of the electrical system and reduced risk of oxidizing materials of the device or tissue of the patient, the counter electrode may have at least 1.5 times as much surface area as the working electrode, whether as a single common counter electrode or as a total surface area of multiple epidermally-positioned counter electrodes. Further electrical efficiency may be gained in systems that include an electrode pair where the counter electrode has at least 3 times as much surface area as the working electrode, such as at least 5 times as much surface area. In devices that include the counter electrode on the sensor flex, the sensor flex needs to be sized toDocket No. : A0010697WO01 / 1277- 125 WOO 1 fit the relatively large counter electrode, which may reduce patient comfort and present challenges in pinpointing the location of the sensor in the patient’s body. Additionally, or alternatively, the counter electrode may be electrically undersized to fit on the sensor flex in a monitor which positions the counter electrode on the sensor flex.

[0043] Monitors according to the present disclosure may allow for increased electrical efficiency by positioning the counter electrode on an epidermal layer of the patient, where the surface area of the counter electrode may be sized for more optimal electrical efficiency and / or reduced power consumption. In some examples, the counter electrode may be wafer-shaped and may be included on the bottom of a monitor housing which contains the electronics of the monitor. In this way, the relatively large counter electrode (e.g., having at least as much surface area as the working electrode) can be positioned in a location that allows for electrically optimal sizing and minimal impact on patient comfort relative to a monitor that positions the counter electrode on the sensor flex. For example, monitors of the present disclosure may have a counter electrode that has at least 1.5 times as much surface area as the working electrode, such as 3 times as much surface area as the working electrode, or at least 5 times as much surface area as the working electrode.

[0044] The bottom of the monitor housing may be fitted with a dermal adhesion which attaches the monitor housing to the patient’s skin. In some examples, the counter electrode may be part of the dermal adhesion. In some examples, the counter electrode may be separate from the dermal adhesion. As a relatively thin (e.g., less than 3 millimeters) layer on the bottom of the monitor housing ex vivo, the counter electrode may be better positioned for patient comfort relative to a subcutaneous counter electrode, since the patient already must wear the monitor housing on their body. In other examples, the epidermally-positioned counter electrode may be displaced from the monitor (e.g., continuous glucose monitor). For example, the counter electrode may be worn in a separate location from the housing and connected to the continuous glucose monitor by one or more electrical conductors.

[0045] Devices which position the counter electrode on an epidermal layer of the patient and the working electrode subcutaneously within interstitial fluid may deliver a current between the electrode pair through the skin of the patient. The current is an example of the electrical signal used to determine analyte level. For instance, a chemical reaction, selective ion exchange, electrostatic interaction, or other interaction between the analyte and the working electrode causes current flow between the electrode pair.

[0046] The patient’s skin may present increased resistance in the electrical circuit of the sensor relative to a device which positions both the working electrode and the counter electrode under the patient’s skin. The presence of the patient’s skin between the electrode pair may causeDocket No. : A0010697WO01 / 1277- 125 WOO 1 one or more of increased noise, reduced electrical signal, reduced signal-to-noise ratio, and / or reduced voltage in the circuit.

[0047] In some examples, devices of the present disclosure may address one or more of the challenges presented by the increased space between the electrode pair and the position of the patient’s skin between the electrode pair. For example, monitors of the present disclosure may employ a filter on the electrical signal. The filter may be digital or analog, or the generated voltage may be maintained at a level (e.g., less than 1 volt) such that the double layer capacitance of the patient’s body may act as a low-pass filter.

[0048] In some examples, to account for skin resistance, devices according to the present disclosure may include processing circuitry which executes a skin resistance module. The skin resistance module may manipulate the electrical signal received from the sensor to account for the skin resistance. In some examples, the skin resistance module may execute a low-pass filter, a high-pass filter, or both. For instance, the low-pass filter may be set at a noise cutoff frequency, which may be the minimum frequency of the noise. In some examples, the skin resistance module may execute a combination low-pass filter and high-pass filter. For instance, to execute the skin resistance module, the processing circuitry may compare the received electrical signal at a point in time to a previously received electrical signal at an immediately previous point in time, and may remove the received electrical signal if the received electrical signal differs in magnitude from a magnitude of the previously received electrical signal by greater than a threshold amount. In this way, by filtering one or more data points from the electrical signal, devices according to the present disclosure may account for increased resistance in the electrical circuit by the positioning of the electrode pair on opposite sides of the patient’s skin. As such, devices which include a counter electrode positioned on an epidermal layer of the patient may detect the level of an analyte over the entire biological range, even with the increased resistance of the skin.

[0049] Devices of the present disclosure are described primarily with respect to continuous glucose monitors. Other monitors configured to sense other analytes are also considered.

[0050] FIG. 1 is a conceptual diagram illustrating an example system 110 that includes an implantable medical device (IMD) configured to measure the glucose levels of a patient in accordance with one or more examples described in this disclosure. FIG. 1 illustrates system 110 that includes insulin pump 114, tubing 116, infusion set 118, monitor 100 (e.g., a glucose level monitoring device comprising a glucose sensor), and patient device 124. Insulin pump 114 may be described as a tethered pump, because tubing 116 tethers insulin pump 114 to infusion set 118. In some examples, rather than utilizing a tethered pump system comprising insulin pump 114, tubing 116, infusion set 118, and / or monitor 100, patient 112 may utilize a patch pump. InsteadDocket No. : A0010697WO01 / 1277- 125 WOO 1 of delivering insulin via tubing and an infusion set, a pump patch may deliver insulin via a cannula extending directly from an insulin pump. In some examples, a glucose sensor may also be integrated into such an insulin pump (e.g., a so-called “all-in-one (AIO) insulin pump”).

[0051] Patient 112 may be diabetic (e.g., Type 1 diabetic or Type 2 diabetic), and therefore, the glucose level in patient 112 may be controlled with delivery of supplemental insulin. For example, patient 112 may not produce sufficient insulin to control the glucose level or the amount of insulin that patient 112 produces may not be sufficient due to insulin resistance that patient 112 may have developed.

[0052] To receive the supplemental insulin, patient 112 may carry insulin pump 114 that couples to tubing 116 for delivery of insulin into patient 112. Infusion set 118 may connect to the skin of patient 112 and include a cannula to deliver insulin into patient 112. Monitor 100 may also be coupled to patient 112 to measure glucose level in patient 112. Insulin pump 114, tubing 116, infusion set 118, and monitor 100 may together form an insulin pump system.

[0053] Monitor 100 may include a glucose sensor with a working electrode that is inserted under the skin of patient 112 and positioned on a sensor flex (e.g., in vivo), such as near the stomach of patient 112 or in the arm of patient 112 (e.g., subcutaneous connection), and a counter electrode that is positioned on an epidermal layer of the patient (e.g., attached to the skin under a monitor housing). The glucose sensor of monitor 100 may be configured to measure the interstitial glucose level, which is the glucose found in the fluid between the cells of patient 112. Monitor 100 may be configured to continuously or periodically sample the glucose level and rate of change of the glucose level over time.

[0054] In one or more examples, insulin pump 114, monitor 100, and / or the various components illustrated in FIG. 1, may together form a closed-loop therapy delivery system. For example, patient 112 may set a target glucose level, usually measured in units of milligrams per deciliter (mg / dL), on insulin pump 114. Insulin pump 114 may receive the current glucose level from monitor 100 and, in response, may increase or decrease the amount of insulin delivered to patient 112. For example, if the current glucose level is higher than the target glucose level, insulin pump 114 may increase the insulin. If the current glucose level is lower than the target glucose level, insulin pump 114 may temporarily cease delivery of the insulin. Insulin pump 114 may be considered as an example of an automated insulin delivery (AID) device. Other examples of AID devices may be possible, and the techniques described in this disclosure may be applicable to other AID devices.

[0055] Insulin pump 114 and monitor 100 may be configured to operate together to mimic some of the ways in which a healthy pancreas works. Insulin pump 114 may be configured to deliver basal dosages, which are small amounts of insulin released continuously throughout theDocket No. : A0010697WO01 / 1277- 125 WOO 1 day. There may be times when glucose levels increase, such as due to eating or some other activity that patient 112 undertakes. Insulin pump 114 may be configured to deliver bolus dosages on demand in association with food intake or to correct an undesirably high glucose level in the bloodstream. In one or more examples, if the glucose level rises above a target level, then insulin pump 114 may deliver a bolus dosage to address the increase in glucose level.Insulin pump 114 may be configured to compute basal and bolus dosages and deliver the basal and bolus dosages accordingly. For instance, insulin pump 114 may determine the amount of a basal dosage to deliver continuously and then determine the amount of a bolus dosage to deliver to reduce glucose level in response to an increase in glucose level due to eating or some other event.

[0056] Accordingly, in some examples, monitor 100 may sample glucose levels for determining rate of change in glucose level over time. Monitor 100 may output the glucose level to insulin pump 114 (e.g., through a wireless link connection like Bluetooth). Insulin pump 114 may compare the glucose level to a target glucose level (e.g., as set by patient 112 or a clinician) and adjust the insulin dosage based on the comparison. In some examples, insulin pump 114 may adjust insulin delivery based on a predicted glucose level (e.g., where glucose level is expected to be in the next 30 minutes).

[0057] As described above, patient 112 or a clinician may set one or more target glucose levels on insulin pump 114. There may be various ways in which patient 112 or the clinician may set a target glucose level on insulin pump 114. As one example, patient 112 or the clinician may utilize patient device 124 to communicate with insulin pump 114. Examples of patient device 124 include mobile devices, such as smartphones, tablet computers, laptop computers, and the like. In some examples, patient device 124 may be a special programmer or controller (e.g., a dedicated remote-control device) for insulin pump 114. Although FIG. 1 illustrates one patient device 124, in some examples, there may be a plurality of patient devices. For instance, system 110 may include a mobile device and a dedicated wireless controller, each of which is an example of patient device 124. For ease of description only, the example techniques are described with respect to patient device 124 with the understanding that patient device 124 may be one or more patient devices.

[0058] Patient device 124 may also be configured to interface with monitor 100. As one example, patient device 124 may receive information from monitor 100 through insulin pump 114, where insulin pump 114 relays the information between patient device 124 and monitor 100. As another example, patient device 124 may receive information (e.g., glucose level or rate of change of glucose level) directly from monitor 100 (e.g., through a wireless link).Docket No. : A0010697WO01 / 1277- 125 WOO 1

[0059] In one or more examples, patient device 124 may comprise a user interface with which patient 112 or the clinician may control insulin pump 114. For example, patient device 124 may comprise a touchscreen that allows patient 112 or the clinician to enter a target glucose level. Additionally, or alternatively, patient device 124 may comprise a display device that outputs the current and / or past glucose level. In some examples, patient device 124 may output notifications to patient 112, such as notifications if the glucose level is too high or too low, as well as notifications regarding any action that patient 112 needs to take. In some examples, monitor 100 and insulin pump 114 of an insulin pump system may be packaged together such that an electrochemical cell or working electrode of the glucose sensor may be placed relatively near an insulin delivery site on the patient.

[0060] The glucose sensor of monitor 100 include a working electrode and a counter electrode. The working electrode and the counter electrode form an electrode pair which interacts with (e.g., chemically reacts with) an analyte and generate a change in an electrical signal. The electrical signal may include, for example, a voltage, an electrical current, or an impedance. In general, the electrical current flowing through a working electrode of the glucose sensor of monitor 100 is indicative of the glucose level in the patient’s interstitial fluid. For example, the electrical signal may be proportional to the concentration of glucose in an interstitial fluid layer of patient 112. In some examples, the working electrode may be part of an electrochemical cell configured to measure voltage, current as an interstitial signal (i Sig), or impedances. In some examples, the glucose sensor of monitor 100 may use the working electrode to sense glucose values in a patient. The working electrode may be positioned on a sensor flex of monitor 100.

[0061] Processing circuitry of monitor 100 may sense glucose levels in a patient by measuring an operating parameter of the working electrode of the glucose sensor of monitor 100 and determining a glucose value from the measured operating parameter. For example, processing circuitry may measure the amount of electrical current flowing through the working electrode, where different amounts of current are indicative of different glucose values in a patient. The relation between electrical current and glucose values may be represented by a formula in memory of monitor 100. The formula may include one or more factors, including one or more calibration factors. The processing circuitry may be configured to measure the one or more calibration factors. A pre-calibration value may be a calibration factor measured by processing circuitry at the time of manufacture / assembly of monitor 100. Alternatively, or in addition, a calibration value may be a calibration factor measured by processing circuitry at the time of installation of glucose monitor 100 on a patient. When processing circuitry measures a new calibration factor, it may calibrate the glucose values sensed by the one or more workingDocket No. : A0010697WO01 / 1277- 125 WOO 1 electrodes by replacing an old calibration factor in the formula with the new calibration factor. In this way, processing circuitry may update the calibration of monitor 100 based on the actual environment monitor 100 will be operating in, rather than relying solely on a calibration made at the time of assembly, manufacture, or initial calibration.

[0062] Processing circuitry may measure a calibration factor for one or more electrodes by measuring an operating parameter of the one or more electrodes and determining a glucose value from the measured operating parameter using the formula in memory. Processing circuitry may compare the determined glucose value to a known or given glucose value. Processing circuitry may determine what calibration factor is necessary (the measured calibration factor), when implemented in the formula, to arrive at the known or given glucose value.

[0063] Processing circuitry of the system which includes monitor 100 may be configured to measure one or more pre-calibration values of an operating parameter of one or more electrodes of monitor 100 at the time of manufacture / assembly of monitor 100. The processing circuitry may then store the pre-calibration values in a memory of the system. Before or during installation of monitor 100, the processing circuitry may measure one or more calibration values of the same operating parameter of one or more monitor electrodes of monitor 100. Processing circuitry may retrieve the one or more pre-calibration values from memory and determine one or more delta values using the one or more pre-calibration values and the one or more calibration values.

[0064] In accordance with one or more examples of the present disclosure, the glucose sensor of monitor 100 includes a counter electrode positioned on an epidermal layer of patient 112. The location of the counter electrode of the glucose sensor on an epidermal layer of patient 112 may allow for one or more components of monitor 100 to be made smaller than these one or more components would otherwise be if the counter electrode was positioned on the sensor flex. For examples, the sensor flex of the glucose sensor of monitor 100 may be relatively smaller in length and / or diameter, which may improve the comfort of patient 112 while wearing monitor 100. Additionally, or alternatively, the smaller size of the sensor flex of the glucose sensor of monitor 100 may allow patient 112 to wear monitor 100 for a longer period of time than would otherwise be possible because the site on patient 112 of monitor 100 may become relatively less irritated by the presence of monitor 100. As such, monitor 100 may be easier to maintain or may provide more continuous management of diabetes than a monitor which includes a glucose sensor that has a counter electrode positioned on a sensor flex or otherwise worn by patient 112 below the skin.

[0065] In some examples, the glucose sensor of monitor 100 includes a working electrode that is covered by a catalytic agent that reacts with glucose in the interstitial fluid of patient 112 to generate the electrical signal received by monitor 100. For example, the glucose sensor ofDocket No. : A0010697WO01 / 1277- 125 WOO 1 monitor 100 may be an enzyme-based working electrode, which may include glucose oxidase (GOx), or glucose dehydrogenase (GDH), or the like, which react with glucose at the working electrode to generate the electrical signal. Alternatively, the working electrode may be a polymer-based working electrode, or may be a metal-based working electrode. In other examples, the interaction between the working electrode and the analyte does not include a chemical reaction. For example, contact between the working electrode and the working electrode may generate the electrical signal or generate a change in the electrical signal that is indicative of the concentration of an analyte of interest.

[0066] In some examples, rather than or in addition to making the sensor flex smaller due to the position of the counter electrode on an epidermal layer of patient 112, monitor 100 may include one or more additional sensors. The working electrode of the additional sensor or sensors may be included on the same sensor flex as the working electrode of the glucose sensor of monitor 100. Each of the additional working electrodes may be covered with a catalytic agent and configured to sense an analyte within patient 112. For example, the additional sensor or sensors may be covered with the same or a different catalytic agent that is configured to react with glucose, which may increase the reliability of the glucose measurement of monitor 100 (e.g., by averaging the measurement of two sensors configured to measure glucose). In some examples, the additional working electrode or working electrodes may be covered with a different catalytic agent which reacts with a different analyte in patient 112. For example, monitor 100 may include a counter electrode on an epidermal layer of patient 112 and a sensor flex that includes a first working electrode covered with a catalytic agent configured to interact with glucose, a second working electrode covered with a catalytic agent configured to interact with a second analyte, and a third working electrode configured to interact with a third analyte. In this way, devices according to the present disclosure may allow for multi-analyte sensing. Information about the levels of the second analyte and / or the third analyte may be used by system 110 alone or in combination with information from the glucose sensor of monitor 100 to tailor or recommend treatment.

[0067] In examples where an additional working electrode or working electrodes are added to the sensor flex, the counter electrode positioned on an epidermal layer of patient 112 may be a counter electrode that is common to each of the sensors of monitor 100. Stated similarly, the external counter electrode may be shared by each of the sensors, which each have their own working electrode. Since space on the epidermal layer may not be as limited as it is on the sensor flex, the counter electrode may be sized such that optimal or nearly optimal electrical efficiency may be achieved. Alternatively, more than one counter electrode may be positioned on an epidermal layer of patient 112.Docket No. : A0010697WO01 / 1277- 125 WOO 1

[0068] FIG. 2 is a conceptual cross-sectional view of an example monitor 200. Monitor 200 is positioned on patient 212 and is configured to monitor a level of an analyte of patient 212. Monitor 200 includes monitor housing 220 which contains electronics and processing circuitry of monitor 200. Monitor housing 220 is adhered to external surface 216 of epidermal layer 214 of patient 212 by dermal adhesion 222. Epidermal layer 214 is positioned above dermal layer 217, which is positioned above interstitial fluid layer 218 of patient 212. In some examples, dermal layer 217 and interstitial fluid layer 218 may be the same layer of patient 212 (e.g., a dermal layer of the skin). In some examples, as illustrated, interstitial fluid layer 218 may be a layer of subcutaneous tissue below the dermis 217 of patient 212.

[0069] Monitor 200 further includes sensor 230. Sensor 230 includes counter electrode 232, working electrode 234, and reference electrode 236. As such, sensor 230 is configured as a three-wire sensor. Monitor 200 includes sensor 230 which has both counter electrode 232 and working electrode 234 positioned on sensor flex 240. Therefore, monitor 200 is illustrated for comparison to devices of the present disclosure, where counter electrode 232 is positioned on epidermal layer 214 of patient 212. Counter electrode 232 need not necessarily be positioned on epidermal layer 214. For example, counter electrode may be positioned on or in contact with dermal layer 217, interstitial fluid layer 218, or both.

[0070] Monitor 200 includes sensor flex 240. Sensor flex 240 extends along length Li from first end 242 connecting sensor flex 240 to monitor housing 220 at external surface 216 of epidermal layer 214 to second end 244 in interstitial fluid layer 218. In some examples, interstitial fluid layer 218 may be a layer of subcutaneous tissue forming the deepest layer of the patient’s skin. In such examples, length Li may be in a range of from about 1 millimeters (mm) to about 6 mm, such as from about 2 mm to about 4 mm. “About,” as used herein, as used herein, encompasses values within ten, twenty, or thirty percent of the stated value. In some examples, length Li of sensor flex 240 may cause irritation or discomfort to patient 112, and / or may penetrate so deeply into interstitial fluid layer that no additional length may be added to make room for additional working electrodes of additional sensors configured to sense the level of a different analyte.

[0071] FIG. 3 is a conceptual cross-sectional view of an example monitor 300, in accordance with one or more examples of the present disclosure. Monitor 300 may be an example of monitor 100 of FIG. 1. Monitor 300 of FIG. 3 may be generally described similarly to monitor 100 of FIG. 1 and monitor 200 of FIG. 2, except where differing as described below. Similar reference numerals indicate similar elements.

[0072] Monitor 300 includes monitor housing 320, sensor flex 340, and sensor 330. Unlike monitor 200, monitor 300 of FIG. 3 includes counter electrode 332 of sensor 330 that is notDocket No. : A0010697WO01 / 1277- 125 WOO 1 positioned on sensor flex 340 but is rather positioned on epidermal layer 314 of patient 312. In the illustrated example, counter electrode 332 is positioned between the bottom of monitor housing 320 and external surface 316 of epidermal layer 314. In some examples, as illustrated, counter electrode 332 may be a discrete, separate component of monitor 300, different from monitor housing 320 and dermal adhesion 322. In some examples, counter electrode 332 may be part of (e.g., integral with) dermal adhesion 322 and / or monitor housing 320.

[0073] Counter electrode 332 may include any suitable material for the electrical circuit. In some examples, counter electrode 332 may comprise one or more of carbon, platinum, gold, silver, or copper. In examples where counter electrode is part of dermal adhesion 322, dermal adhesion 322 may include a conductive adhesive. For example, dermal adhesion 322 may include electrically conductive particles dispersed in an adhesive polymer or polymers that may also be stretchable like TPU (thermoplastic polymer). In some examples, additional electrically conductive layers may be included (not pictured), such as a primer layer or the like. In some examples, dermal adhesion 322 may include a silver chloride paste.

[0074] Counter electrode 332 may define a relatively thin (e.g., from about 0.05 mm to about 2 mm) layer at the bottom of monitor housing 320. In some examples, counter electrode 332 may substantially match the footprint of monitor housing 320, which may allow for increased surface area without impacting wearability of monitor 300. In some examples, counter electrode 332 may define a wafer shape. In such examples, counter electrode 332 may define a circular perimeter, and sensor flex 340 may extend into patient 312 from the center of the defined circle. Shaping counter electrode 332 in this way may allow for sufficient surface area from counter electrode 332 to electrically interact with working electrode 334 without generating a voltage which could be dangerous to monitor 300 or the surrounding tissue, while simultaneously reducing or minimizing deleterious impacts on the standoff height or footprint of monitor 300. In some examples, counter electrode 332 may have surface area that is at least the same size as the surface area of working electrode 334, such as at least about 1.5 times larger than working electrode 334, such as at least about 1.7 times larger than working electrode 334, or at least about 3.0 times larger than working electrode 334. The relatively large surface area of counter electrode 332 may improve electrical efficiency and reduce power consumption of monitor 300.

[0075] Moreover, monitor 300 of FIG. 3, which includes external counter electrode 332 as part of sensor 330, may have one or more components that are reduced in size relative to monitor 200 of FIG. 2, which includes internal counter electrode 232 positioned on sensor flex 240. For example, sensor flex 340 may extend along length L2 from first end 342 to second end 344. Length L2 may be between about may be in a range of from about 0.5 mm to about 2.0 mm. As illustrated, monitor 300 may, in some examples, penetrate less than about halfway throughDocket No. : A0010697WO01 / 1277- 125 WOO 1 interstitial fluid layer 318. The relatively shorter length of sensor flex 340 may increase patient comfort of patient 312 while wearing monitor 300 relative to monitor 200 of FIG. 2.Additionally, or alternatively, the reduced size of the transcutaneous components of monitor 300 may reduce irritation of tissue surrounding monitor 300, thus reducing the need to remove monitor 300 as frequently as would otherwise be required with monitor 200 of FIG. 2.

[0076] FIG. 4 is a conceptual cross-sectional view of an example monitor 400, in accordance with one or more examples of the present disclosure. Monitor 400 may be an example of monitor 100 of FIG. 1. Monitor 400 of FIG. 4 may be generally described similarly to monitor 100 of FIG. 1, monitor 200 of FIG. 2, and monitor 300 of FIG. 3, except where differing as described below. Similar reference numerals indicate similar elements.

[0077] Monitor 400 is configured as a multi-analyte monitor. As such, monitor 400 includes first sensor 430A. First sensor 430A includes counter electrode 432A, working electrode 434A, and reference electrode 436A. First sensor 430A may be configured to sense a first analyte, which may be glucose. Monitor 400 also includes second sensor 430B. Second sensor 430B includes counter electrode 432B, working electrode 434B, and reference electrode 436B. Second sensor 430 A may be configured to sense a second analyte, which may be insulin, creatinine, ketones, lactate, alcohol, sodium, potassium, hydrogen ions, hydroxide ions, oxygen or chloride. Monitor 400 also includes third sensor 430C. Third sensor 430C includes counter electrode 432C, working electrode 434C, and reference electrode 436C. Third sensor 430C may be configured to sense a third analyte, which may be potassium or any of the above-mentioned analytes. Counter electrodes 432A, 432B, and 432C are part of single common counter electrode 432 positioned on external surface 416 of epidermal layer 414 of patient 412.

[0078] Sensor flex 440 of monitor 400 extends along length Li from first end 442 to second end 444. As illustrated, length Li of the sensor flex 440 of monitor 400 is equal to length Li of sensor flex 240 of FIG. 2. Thus, in the illustrated example, monitor 400, which positions counter electrode 432 on epidermal surface 414 of patient 412, may allow for sensing of a second analyte and a third analyte, each of which is different than the first analyte, without increasing the size (e.g., diameter or length) of a similar monitor which positions the counter electrode on the sensor flex. With the electrical signals indicative of the second analyte from second sensor 430B and the third analyte from third sensor 430C, monitor 400 may provide more information about the physiological conditions of patient 400 than a single analyte sensor. The additional information may be used by processing circuitry of monitor 400 to tailor treatment strategies, without requiring a larger sensor flex or additional monitoring devices located at different monitoring sites.Docket No. : A0010697WO01 / 1277- 125 WOO 1

[0079] FIG. 5 is a conceptual cross-sectional view of an example monitor 500, in accordance with one or more examples of the present disclosure. Monitor 500 may be an example of glucose monitor 100 of FIG. 1. Monitor 500 of FIG. 5 may be generally described similarly to glucose monitor 100 of FIG. 1, monitor 200 of FIG. 2, monitor 300 of FIG. 3, and monitor 400 of FIG. 4, except where differing as described below. Similar reference numerals indicate similar elements.

[0080] Monitor 500 is a multi-analyte sensor similar to monitor 400, except that sensors 530 A, 530B, and 530C are configured as 2-wire sensors rather than the 3 -wire sensors of monitor 400. As such, monitor 500 does not include any reference electrodes. Instead, sensors 530A, 530B, and 530C are supplied with power and signal their state through only counter electrodes 532A, 532B, and 532C, and working electrodes 534A, 534B, and 534C. Arranging one or more of sensors 530A, 530B, and / or 530C as a two-wire sensor may advantageously improve ease of wiring and / or may be more compact with the limited space on sensor flex 540, through the omission of reference electrodes.

[0081] FIG. 6 is a cross-sectional view of an example monitor 600, which includes a glucose monitor and insulin pump. In the example shown, monitor 600 includes a glucose monitor and an insulin delivery device packaged together. Monitor 600 may be an example of monitor 100 of FIG. 1.

[0082] Monitor 600 may inserted into a patient (112, FIG. 1) a single time and include both insulin delivery and glucose monitoring functionalities, e.g., so that patient 112 does not need to have two different devices inserted, e.g., two different insertions. In the example shown, monitor 600 includes monitor housing 620, sensor flex 640, and delivery lumen 650 (e.g., which is an example cannula coupled to an infusion pump within medical device 600). Monitor housing 620 may be configured to house the glucose monitor (not shown) and the insulin pump (not shown), such that sensor flex 640 and delivery lumen 650 may be inserted into patient 112 and separated laterally.

[0083] Sensor flex 640 includes analyte sensors 630A, 630B, and 630C. In the example shown, sensor flex 640 includes three working electrodes 634A, 634B, and 634C. Each of the individual working electrodes forms an electrode pair with common counter electrode 632. In some examples, common counter electrode 632 may be attached to or part of delivery lumen 650 (in addition to or instead of the external counter electrode). In this way, three separate sensors 630A, 630B, and 630C, e.g., working-counter electrode pairs providing three separate sensor signals may be formed. For example, counter electrode 632 and working electrode 634A may form an electrode pair that makes up sensor 630A, counter electrode 632 and working electrode 634B may form an electrode pair that makes up sensor 630B, and counter electrode 632 and working electrode 634C may form an electrode pair that makes up sensor 630C. Sensor flex 640Docket No. : A0010697WO01 / 1277- 125 WOO 1 may optionally include one or more reference electrodes if it is desired to arrange one or more of the sensors as a three-wire sensor. Sensor flex 640 may be connected to the electronics within monitor housing 620.

[0084] Delivery lumen 650 may be connected to an infusion set and / or an insulin pump housed within monitor housing 620, and may be configured to deliver insulin through an aperture in fluid communication with a lumen of delivery lumen 650 and inserted within patient 112. In the example shown, delivery lumen 650 may output the fluid at distal end 652. As illustrated, devices according to the present disclosure may be integrated into an “all-in-one” device which is configured to both monitor an analyte level and deliver treatment.

[0085] FIG. 7 is a block diagram illustrating components of monitor 700. For instance, FIG.7 is a block diagram of sensor electronics device 730 according to an example of the disclosure. Monitor 300 (FIG. 3), monitor 400 (FIG. 4), monitor 500 (FIG. 5), and / or monitor 600 (FIG. 6) may include one or more processors configured to perform example techniques, although the techniques will primarily be described with respect to monitor 400 of FIG. 4. Sensor electronics device 730 may be part of the one or more processors. In one or more examples, the monitor may be considered as including the electrodes used for determining the analyte level. Sensor electronics device 730 may be configured to determine the level of one or more analytes. Sensor electronics device 730 may be connected to one or more sensors (430 A, 430B, 430C, FIG. 4). Each individual sensor may include a biomolecule or some other catalytic agent, and may be placed in a human body in a vascular or non-vascular environment. For example, working electrodes 434A, 434B, 434C may be placed in interstitial layer 418, or in a vein and be subjected to a blood stream, or may be placed in a subcutaneous or peritoneal region of the human body. The sensors may share common counter electrode 432, which may be positioned on epidermal layer 414 of patient 412.

[0086] Sensor electronics device 730 may include measurement processor 732, display and transmission unit 734, controller 736, power supply 738, and memory 740.In examples of the disclosure, measurement processor 732, display and transmission unit 734, and controller 736 may be formed as separate semiconductor chips. However, other examples may combine measurement processor 732, display and transmission unit 734, and controller 736 into a single or multiple customized semiconductor chips. In general, measurement processor 732 may be configured to receive a current, voltage, and / or impedance from sensors 430A, 430B, 430C. Each of the sensors may generate an electrical signal or generate a change in an electrical signal which is indicative of a level (e.g. a concentration) of an analyte being measured. The sensors may generate the electrical signal indicative of the same analyte as the other sensors or a different analyte. For example, sensor 430 A may generate an electrical signal may be indicativeDocket No. : A0010697WO01 / 1277- 125 WOO 1 of a glucose level. The sensor signal may be measured at a working electrode 434A. In an example of the disclosure, the sensor signal may be a current (e.g., iSig) measured at the working electrode 434A. In another example of the disclosure, the sensor signal may be a voltage measured at the working electrode 434A of the sensor electrodes.

[0087] Measurement processor 732 receives the sensor signal (e.g., a measured current, voltage, and / or impedance) after the sensor signal is measured at the electrode (e.g., working electrode 434A). Measurement processor 732 may receive the sensor signal and calibrate the sensor signal utilizing reference values. For example, measurement processor 732 may calibrate the sensor signal utilizing reference values based on a known analyte quantity, e.g., a zeroanalyte measurement to determine a baseline sensor signal. In some examples, changes to the sensor over time may change the responsivity of the sensor, changing the sensor signal and measurement accuracy. Measurement processor 732 may utilize the reference values to adjust for changes over time. In an example of the disclosure, the reference values are stored in a reference memory (e.g., memory 740) and provided to measurement processor 732. Based on the sensor signals and the reference values, measurement processor 732 may determine an analyte measurement. Measurement processor 732 may store the analyte measurements in memory 740. The sensor measurements may be sent to display and transmission unit 734 to be either displayed on a display in or transmitted to an external device. Sensor 430B and sensor 430C may operate similarly to measure, record, store, display, and / or transmit the level of different analytes (e.g., sensor 430A senses glucose, sensor 430B senses lactate, and sensor 430C senses potassium).

[0088] Memory 740 may be any type of memory device and may be configured to store measurements produced by measurement processor 732, reference values used to determine glucose measurements from sensor signals, or other data used and / or produced by measurement processor 732 and / or controller 736. In some examples, memory 740 may further store software and / or firmware that is executable by measurement processor 732 and / or controller 736. For example, memory 740 may store skin resistance module 742, which may store instructions that, when executed, manipulate the measurements produced by measurement processor 732 to account for the epidermal position of counter electrode 432. Since positioning counter electrode 432 on epidermal layer 414 may increase the resistance in the electrical circuit of sensor 430A relative to a sensor which includes both electrodes adjacent to each other on sensor flex 440, skin resistance module 742 may execute one or more post-processing steps to filter or otherwise manipulate the measurements to account for the increased resistance, as will be further explained below.Docket No. : A0010697WO01 / 1277- 125 WOO 1

[0089] Sensor electronics device 730 may be a single analyte or a multi-analyte monitor which includes a display to display one or more analyte level readings. However, such displays may not be needed, such as in examples where the display is provided by patient device 124.

[0090] Power supply 738 may be a battery. In other examples, different battery chemistries may be utilized, such as lithium-based chemistries, alkaline batteries, nickel metal hydride, or the like, and a different number of batteries may be used. Sensor electronics device 730 provides power to electrodes via power supply 738 through a cable and a cable connector.

[0091] Controller 736 may be a processor, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or any other equivalent integrated or discrete logic circuitry. In some examples controller 736 may be configured to cause a specific voltage or current to be output to analyte sensors 430A, 430B, 430C. Sensors 430A, 430B, 430C may receive the voltage level or value, which may be the same or different for each sensor. With reference to FIGS. 7 and 8, in an example of the disclosure, working electrodes 832A, 832B, and 832C of sensors 830A, 830B, and 830C, respectively, may receive the reference voltage from power supply 738. The application of the voltage level VSET may cause sensors 830 A, 830B, and 830C to create a sensor signal (iSig) 857A, 857B, 857C between their respective working electrode and common counter electrode 832, which is positioned on external surface 816 of the patient’s skin (illustrated schematically in FIG. 8 by the thick horizontal line). Each of the individual iSig values may be indicative of a level of a different analyte being measured.

[0092] FIG. 8 is a block diagram illustrating example sensors 830A, 830B, and 830C in accordance with one or more examples of the present disclosure. In the schematic illustration of FIG. 8, power supply 738 under control of controller 736 may apply a bias voltage to each of first sensor 830 A, second sensor 830B, and third sensor 830C. In the example shown, sensors 830 A, 830B, and 830C share common counter electrode 832 and common reference electrode 836. Counter electrode 832 in positioned on an epidermal layer of the patient’s skin, as illustrated in FIGS. 3-6. In the example in FIG. 6, an operational amplifier (op amp) 870 or other servocontrolled device may connect to the sensors through a circuit / electrode interface 8722. Op amp 870, utilizing feedback through the sensors, maintains a prescribed voltage between reference electrode 836 and working electrodes 834A, 834B, 834C (e.g., VSET) by adjusting the voltage at counter electrode 832. In some examples, the voltage at reference electrode 836 is from about -1000 mV to about 1000 mv. In some examples, a positive voltage may cause a current to be source at counter electrode 832 and sunk at working electrodes 834A, 834B, 834C, while a negative voltage may cause a current to be sourced at working electrodes 834A, 834B, 834C, and sunk at counter electrode 832. As described above, working electrode 834A may be covered withDocket No. : A0010697WO01 / 1277- 125 WOO 1 a first catalytic agent, and as such may be configured to interact with a first analyte, working electrode 834B may be covered with a second catalytic agent configured to interact with a second analyte, and working electrode 834C may be covered with a third catalytic agent configured to interact with a third analyte. Additionally, or alternatively, one or more of the working electrodes may be covered with a selective ion membrane which allows only a certain type of ion to contact the working electrode.

[0093] In an example sensing mode operation, current 857A may flow from counter electrode 832 to working electrode 834A, current 857B may flow from counter electrode 832 to working electrode 834B, and current 857C may flow from counter electrode 832 to working electrode 834C. Counter electrode 832 balances the chemical reactions that are occurring at working electrodes 834A, 834B, 834C. Measurement processor 732 of FIG. 7 may measure current 857 to determine the electrochemical reaction between the sensor electrodes. The circuitry disclosed in FIG. 8 may be utilized in a long-term or implantable sensor or may be utilized in a short-term or subcutaneous sensor.

[0094] In this way, sensor electronics device 730 may monitor an electrical parameter of the electrical chemical cell, e.g., an electrical current that is proportional to the impedance of the electrochemical cell such as current 857A. For example, measurement processor 732 may provide a sensor signal to controller device 736. In one example, the sensor signal is a current 857A through a working electrode 834A of sensor 830A. Controller 736 may accumulate values for current 857A over a period of time and may calculate a rate of change of the current values. For example, controller 736 may calculate the slope of a plot of the current.

[0095] In some examples, controller 736 may accumulate and measure changes in electrochemical impedance spectroscopy (EIS) (real and imaginary impedance at different frequencies), voltage at counter electrode 832, and / or current through a background electrode. A background electrode is similar to a working electrode, but may not include a catalytic layer for breaking down and sensing an analyte. Like current through working electrode 834A, larger slopes / changes in these other sensor signals may indicate a need for a higher VSET, while lower slopes / changes in these other sensor signals may indicate a need for a lower VSET at working electrode 834A. In this way, sensor electronics device 730 may be configured to monitor EIS, voltage, and / or current through a background electrode similar to monitoring current 857A as described herein.

[0096] Returning to FIG. 7, as discussed above, due to the increased resistance in the circuit stemming from the external position of counter electrode 832, measured analyte levels by measurement processor 732 may calculate measured analyte levels that are relatively noisy when compared to those values measured by a device that includes an internal counter electrode. AsDocket No. : A0010697WO01 / 1277- 125 WOO 1 such, either of measurement processor 732 and / or controller 736 may execute skin resistance module 742 to account for the epidermal position of counter electrode 832. Although skin resistance module 742 is illustrated as software that executes on measurement processor 732 and / or controller 736, in some examples, skin resistance module may be fixed-function circuitry that is formed within measurement processor 732 and / or controller 736 or independent of measurement processor 732 and / or controller 736. In some examples, skin resistance module 742 may be firmware that measurement processor 732 and / or controller 736 execute.

[0097] In some examples, to execute skin resistance module 742, measurement processor 132 may perform one or more post-processes on the determined analyte measurement before storing the value in memory 740. For example, measurement processor 732 may remove one or more received values of the current 857A by one or both of a low-pass filter or a high-pass filter.Filtering may reduce or eliminate noise and / or improve the signal to noise ratio. In addition to removing noise from the data, measurement processor 132 may cause controller 136 to take one or more actions. For example, responsive to the presence of noise in current 857A that exceeds a threshold, measurement processor 132 may cause controller 136 to reduce VSET at working electrode 834A.

[0098] In some examples, to execute skin resistance module 742, measurement processor 132 may receive, from sensor 430A, a stream of values of the current 857A, which may be regularly spaced apart in a temporal dimension (e.g., every ten seconds, every 5 minutes, or the like). Skin resistance module 742 may filter one or more data points from stream of received values by comparing the received current 857A at a point in time to a previously received current 857A, such as an immediately previous current 857A, and removing the received current value 857A if the received current 857A differs in magnitude from a magnitude of the previously received current 857A by greater than a threshold amount. In other words, if current 857A unexpectedly spikes or dips in value by more than, for example, 50%, in the space of a single measurement, skin resistance module 742 may discard the data point and not store the received value in memory 740. Additionally, or alternatively, skin resistance module may perform a frequencybased filtering of current 857A. For example, skin resistance module 742 may determine a noise cutoff frequency at a minimum frequency, and may remove one or more data points by comparing current 857A to the determined minimum frequency.Examples

[0099] A series of tests were performed to validate the use of a monitor that includes a sensor which includes a counter electrode positioned on an epidermal surface of a patient. The first test was performed on a pig leg filled with phosphate-buffered saline (PBS). The sensor included an electrode pair including a counter electrode and a working electrode. The working electrode wasDocket No. : A0010697WO01 / 1277- 125 WOO 1 positioned on a sensor flex within an interstitial layer. The counter electrode was tested at three different locations on an epidermal layer of the pig leg and a fourth location on a sensor flex within an interstitial layer. The test was performed to determine whether the external positions of the counter electrode would result in undesirable noise or signal loss, and further to determine whether any of the attachment methods, such as different dermal adhesions, would impact the electrode response. FIG. 9 is a graph illustrating the signal response, with current on the Y-axis and time on the X-axis.

[0100] At time 902, the counter electrode was attached to an epidermal layer of the pig leg using a NIKOTABS® bio-adhesive, which is a silver / silver chloride ECG electrode. The signal response was strong and stable. At time 904, the counter electrode was moved to a second location on the epidermal layer of the pig leg, and the counter electrode was attached using the same NIKOTABS® bio-adhesive, along with Spectra® 360 conductive electrode gel. The signal response was strong and stable, with relatively little noise. At time 906, the counter electrode was moved to a third location on the epidermal layer of the pig leg, and was attached with a SKINTACT® dermal adhesion. Once again, the signal response was strong and stable. Finally, at time 908, the counter electrode was moved to a fourth location, this time to a conventional location within the interstitial layer of the pig leg. The signal response was strong and stable in the fourth location as well. From this test, it was demonstrated that the electrical signal may be generated and captured with relatively little noise, even when the counter electrode is positioned on an epidermal layer of the pig leg.

[0101] A second test was performed on the pig leg. FIG. 10 is a graph illustrating a comparison between a glucose sensor that included a counter electrode that was positioned on an epidermal layer of the pig leg, labeled “External,” and a glucose sensor that included a counter electrode that was positioned within interstitial fluid of the pig leg, labeled “Control,” in response to various injections of glucose. At time 1, an injection of 1.5 milliliters of ~130mg / dL of glucose solution was injected. At time 2, a second injection of 1.5 milliliters of ~130mg / dL of glucose solution was injected. At time 3, an injection of 1.5 milliliters of ~300mg / dL of glucose solution was injected. No difference in noise level was observed between the two sensors. If anything, it was noted that the “control” may even be noisier than “external”. Both sensors responded as expected to glucose and no crosstalk was observed between channels. The difference in glucose response amplitudes was attributed to tissue areas where each sensor was located in the pig leg (“external” had less tissue around it to hold the glucose near the electrode). At one point during the test, the “external” electrode was disconnected and subsequently reconnected, as illustrated. A trajectory line is added in FIG. 10 to account for the time that the electrode was disconnected.Docket No. : A0010697WO01 / 1277- 125 WOO 1

[0102] FIG. 11 is a graph illustrating an example electrical signal generated by an example glucose sensor in response to a series of glucose injections. FIG. 12 is a graph illustrating an example electrical signal generated by the example glucose sensor of FIG. 11 with additional resistance at the counter electrode which mimics the resistance of human skin, in response to the same series of glucose injections. Even with a relatively high resistance relative to a typical patient’s skin, 1.01 megaohms, the three-wire glucose sensor with additional resistance was able to detect glucose over the entire biological range. The current was slightly reduced in amplitude and showed slightly more noise, which may be addressed at least partially by devices and techniques of the present disclosure. The test validated that although the increased resistance presented due to the patient’s skin when moving the counter electrode off of the sensor flex and onto the epidermal layer of the patient, these challenges may be overcome, and the advantages discussed herein may be gained.

[0103] FIG. 13 is a flowchart illustrating an example technique for determining an analyte level in a patient, according to one or more examples of the present disclosure. The technique of FIG. 13 may be performed using glucose monitor 100 of FIG. 1, monitor 300 of FIG. 3, monitor 400 of FIG. 4, monitor 500 of FIG. 5, monitor 600 of FIG. 6, or sensor electronics device 730 of FIG. 7. However, the disclosed device may be used to perform other techniques, and the illustrated technique may be performed with other devices. The illustrated technique is described with concurrent reference to sensor electronics device 730 of FIG. 7 and monitor 400 of FIG. 4.

[0104] Sensor electronics device 730 may generate a voltage (VSET, FIG. 8) between working electrode 434A and counter electrode 432A of sensor 430A. Counter electrode 432A is positioned on an epidermal layer 414 of patient 412. Working electrode 434A may be positioned on sensor flex 440 of monitor 400, which may be inserted into interstitial layer 418 of patient 412. Sensor 430A may be all or a portion of monitor 400.

[0105] Working electrode 434A and counter electrode 432A form an electrode pair. Working electrode 434A may interact (e.g., react) with an analyte within interstitial layer 418 of patient 412. The analyte may be selected by choice of the catalytic agent that is included on working electrode 434A. For example, working electrode may be configured to react with glucose by covering working electrode 434A with glucose oxidase. In other examples, working electrode 434A may not necessarily react with the analyte. For example, working electrode 434A may an ion selective electrode. In such examples, working electrode 434A may be covered with a membrane that allows only a specific ion to pass through the membrane. In any case, working electrode 434A may interact with the analyte in interstitial layer 418. (1302).

[0106] In response to the interaction of the analyte with working electrode 434A, sensor 430A may generate an electrical signal (iSig), which may be current 857A, between workingDocket No. : A0010697WO01 / 1277- 125 WOO 1 electrode 434A and counter electrode 432A (1304). Current 857A may be proportional to the concentration of the analyte at working electrode 434A. As such, the magnitude of current 857A may be indicative of the concentration of the analyte at working electrode 434A, where a stronger current may reflect a higher concentration of the analyte.

[0107] Sensor 430A may output the electrical signal as current 857A, which is indicative of an analyte level of patient 412 (1306). Sensor electronics device 730 may convert the electrical signal into a value representative of the concentration of the analyte within interstitial fluid of a patient. Sensor electronics device may store the value in memory 740, or may output the value via display and transmission unit 734.

[0108] The following describes examples that may be used alone or in combination.

[0109] Example 1 : A device includes a monitor includes a first electrode; and a second electrode, wherein the first electrode and the second electrode form an electrode pair configured to interact with the analyte and generate the electrical signal or generate a change in the electrical signal in response to the interaction, and wherein the second electrode is configured to be positioned on an epidermal layer of the patient.

[0110] Example 2: The device of example 1, wherein the first electrode is configured to be positioned within interstitial fluid of the patient.

[0111] Example 3: The device of example 2, wherein the first electrode is positioned on a sensor flex, wherein the sensor flex is configured to extend from an external surface of the epidermal layer of the patient to an interstitial fluid layer of the patient.

[0112] Example 4: The device of any of examples 1-3, wherein the first electrode is a working electrode, and wherein the second electrode is a counter electrode.

[0113] Example 5: The device of example 4, wherein the sensor further comprises a third electrode, wherein the third electrode is a reference electrode.

[0114] Example 6: The device of example 5, wherein the third electrode is positioned on a sensor flex, wherein the sensor flex is configured to extend from an external surface of the epidermal layer of the patient to an interstitial fluid layer of the patient.

[0115] Example 7: The device of any of examples 1-6, wherein the analyte is at least one of glucose, insulin, creatinine, ketones, lactate, alcohol, sodium, potassium, hydrogen ions, hydroxide ions, oxygen, or chloride.

[0116] Example 8: The device of any of examples 1-7, wherein the sensor is a first sensor, the electrical signal is a first electrical signal, the electrode pair comprises a first electrode pair, the analyte is a first analyte, the device further includes a fourth electrode; and a fifth electrode, wherein the fourth electrode and the fifth electrode form a second electrode pair configured to interact with the second analyte and generate the second electrical signal in response to theDocket No. : A0010697WO01 / 1277- 125 WOO 1 reaction, and wherein the fifth electrode is configured to be positioned on the epidermal layer of the patient.

[0117] Example 9: The device of example 8, wherein the fifth electrode and the second electrode are a common counter electrode.

[0118] Example 10: The device of example 8, wherein the fourth electrode is positioned on the sensor flex.

[0119] Example 11 : The device of example 8, further comprising a sixth electrode, wherein the sixth electrode is a reference electrode.

[0120] Example 12: The device of example 8, further includes a seventh electrode; and an eighth electrode, wherein the seventh electrode and the eighth electrode form a third electrode pair configured to interact with the third analyte and generate the third electrical signal in response to the reaction, and wherein the eighth electrode is configured to be positioned on an epidermal layer of a patient.

[0121] Example 13: The device of example 12, wherein the second electrode, fifth electrode, and the eighth electrode are a common counter electrode.

[0122] Example 14: The device of any of examples 1-13, wherein the second electrode is wafer-shaped.

[0123] Example 15: The device of any of examples 1-14, wherein the second electrode is part of a dermal adhesion.

[0124] Example 16: The device of any of examples 1-15, wherein the second electrode includes one or more of carbon, platinum, gold, or silver.

[0125] Example 17: The device of any of examples 1-16, wherein the sensor comprises processing circuitry, wherein the processing circuitry is configured an output a signal indicative of the analyte level of the patient.

[0126] Example 18: The device of example 17, wherein to output the signal indicative of the analyte level, the processing circuitry is configured to account for an epidermal location of the second electrode, wherein, to account for the epidermal location of the second electrode, the processing circuitry is configured to execute a skin resistance module.

[0127] Example 19: The device of example 18, wherein, to execute the skin resistance module, the processing circuitry is configured to: receive, from the electrode pair, the electrical signal indicative of the analyte level of the patient; filter one or more data points from the electrical signal, wherein to filter one or more data points form the electrical signal, the processing circuitry is configured to: compare the received electrical signal at a point in time to a previously received electrical signal at an immediately previous point in time, and remove theDocket No. : A0010697WO01 / 1277- 125 WOO 1 received electrical signal if the received electrical signal differs in magnitude from a magnitude of the previously received electrical signal by greater than a threshold amount.

[0128] Example 20: The device of any of examples 1-19, wherein the second electrode has at least 1.5 times as much surface area as the first electrode.

[0129] Example 21 : The device of example 13, wherein the common counter electrode has at least as much surface area as the first electrode, the fourth electrode, and the seventh electrode combined.

[0130] Example 22: The device of example 4, wherein the sensor flex is a first sensor flex, and wherein the device further comprises a second sensor flex, at least one electrode positioned on the second sensor flex.

[0131] Example 23 : A method includes interacting an electrode pair which includes a first electrode and a second electrode with an analyte of a patient, wherein the electrode pair is part of a sensor, wherein the sensor is part of a monitor, and wherein the second electrode is positioned on an epidermal layer of the patient, generating an electrical signal or a change in an electrical signal indicative of an analyte level of the analyte between the first electrode and the second electrode in response to the interaction with the analyte, and outputting, from the sensor, the electrical signal indicative of the analyte level of the analyte of the patient.

[0132] Example 24: A non-transitory computer-readable storage medium having stored thereon instructions that, when executed, configure a processor to: interact an electrode pair which includes a first electrode and a second electrode with an analyte of a patient, wherein the electrode pair is part of a sensor, and wherein the sensor is part of a monitor, and wherein the second electrode is positioned on an epidermal layer of the patient, generate an electrical signal or a change in an electrical signal indicative of an analyte level of the analyte between the first electrode and the second electrode in response to the reaction with the analyte, and output, from the sensor, the electrical signal indicative of the analyte level of the analyte of the patient.

[0133] The techniques described in this disclosure may also be embodied or encoded in a computer-readable medium, such as a computer-readable storage medium, containing instructions. Instructions embedded or encoded in a computer-readable medium may cause a programmable processor, or other processor, to perform the method, e.g., when the instructions are executed. Computer-readable media may include non-transitory computer-readable storage media and transient communication media. Computer readable storage media, which is tangible and non-transitory, may include random access memory (RAM), read only memory (ROM), programmable read only memory (PROM), erasable programmable read only memory (EPROM), electronically erasable programmable read only memory (EEPROM), flash memory, a hard disk, a CD-ROM, a floppy disk, a cassette, magnetic media, optical media, or otherDocket No. : A0010697WO01 / 1277- 125 WOO 1 computer-readable storage media. It should be understood that the term “computer-readable storage media” refers to physical storage media, and not signals, carrier waves, or other transient media.

[0134] Such hardware, software, and firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure. In addition, any of the described units, modules or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be realized by separate hardware or software components. Rather, functionality associated with one or more modules or units may be performed by separate hardware or software components, or integrated within common or separate hardware or software components.

[0135] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

Docket No. : A0010697WO01 / 1277- 125 WOO 1 WHAT IS CLAIMED IS:

1. A device comprising:a monitor comprising at least one sensor configured to sense an electrical signal indicative of an analyte level of an analyte of a patient, wherein the sensor comprises:a first electrode; anda second electrode,wherein the first electrode and the second electrode form an electrode pair configured to interact with the analyte and generate a change in an electrical signal in response to the interaction, andwherein the second electrode is configured to be positioned on an epidermal layer of the patient.

2. The device of claim 1, wherein the interaction with the analyte is a chemical reaction, and wherein the chemical reaction is configured to generate the electrical signal.

3. The device of claim 1 or claim 2, wherein the first electrode is configured to be positioned within interstitial fluid of the patient.

4. The device of claim 3, wherein the first electrode is positioned on a sensor flex, wherein the sensor flex is configured to extend from an external surface of the epidermal layer of the patient to an interstitial fluid layer of the patient.

5. The device of any of claims 1-4, wherein the first electrode is a working electrode, and wherein the second electrode is a counter electrode.

6. The device of claim 5, wherein the sensor further comprises a third electrode, wherein the third electrode is a reference electrode.

7. The device of claim 6, wherein the third electrode is positioned on a sensor flex, wherein the sensor flex is configured to extend from an external surface of the epidermal layer of the patient to an interstitial fluid layer of the patient.Docket No. : A0010697WO01 / 1277- 125 WOO 1 8. The device of any of claims 1-7, wherein the analyte is at least one of glucose, insulin, creatinine, ketones, lactate, alcohol, sodium, potassium, hydrogen ions, hydroxide ions, oxygen, or chloride.

9. The device of any of claims 1-8, wherein the sensor is a first sensor, the electrical signal is a first electrical signal, the electrode pair comprises a first electrode pair, the analyte is a first analyte, the device further comprising a second sensor, wherein the second sensor is configured to sense a second electrical signal indicative of a second analyte level of a second analyte of the patient, and wherein the second sensor comprises:a fourth electrode; anda fifth electrode,wherein the fourth electrode and the fifth electrode form a second electrode pair configured to interact with the second analyte and generate a change in the second electrical signal in response to the interaction, andwherein the fifth electrode is configured to be positioned on the epidermal layer of the patient.

10. The device of claim 9, wherein the fifth electrode and the second electrode are a common counter electrode.

11. The device of claim 9 or claim 10, wherein the fourth electrode is positioned on the sensor flex.

12. The device of any of claims 9-11, further comprising a sixth electrode, wherein the sixth electrode is a reference electrode.Docket No. : A0010697WO01 / 1277- 125 WOO 1 13. The device of any of claims 9-12, further comprising a third sensor, wherein the third sensor is configured to sense a third electrical signal indicative of a third analyte level of a third analyte of the patient, and wherein the third sensor comprises:a seventh electrode; andan eighth electrode,wherein the seventh electrode and the eighth electrode form a third electrode pair configured to interact with the third analyte and generate a change in the third electrical signal in response to the interaction, andwherein the eighth electrode is configured to be positioned on an epidermal layer of a patient.

14. The device of claim 13, wherein the second electrode, fifth electrode, and the eighth electrode are a common counter electrode.

15. A method compri sing :interacting an electrode pair which includes a first electrode and a second electrode with an analyte of a patient, wherein the electrode pair is part of a sensor, wherein the sensor is part of a monitor, and wherein the second electrode is positioned on an epidermal layer of the patient,generating an electrical signal indicative of an analyte level of the analyte between the first electrode and the second electrode in response to the interaction with the analyte, and outputting, from the sensor, the electrical signal indicative of the analyte level of the analyte of the patient.

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