Layout of electrochemical multi-sensor

Abstract

Traditionally, the risk or progression of health conditions such as acute kidney injury (AKI) or congenital heart failure (CHF) are evaluated based on laboratory tests. While being worn by a patient, an interstitial patient monitor having a plurality of working electrodes continuously monitors a plurality of analytes in interstitial tissue of a patient. In this way, the interstitial patient monitor can promote early detection of health conditions such as AKI and CHF without laboratory tests.

Description

Attorney Docket No. A0013164W001LAYOUT OF ELECTROCHEMICAL MULTI-SENSORCROSS-REFERENCES TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 703,811, filed October 4, 2024, and U.S. Provisional Patent Application No. 63 / 765,424, filed February 28, 2025, the entire disclosures of which are incorporated herein by reference in their entireties.FIELD

[0002] The disclosure is generally related to electrochemical sensors for medical applications including metabolic monitoring of patients.BACKGROUND

[0003] Many health conditions require blood samples for monitoring, diagnosing, and / or treating patients. For example, the risk or progression of health conditions such as acute kidney injury (AKI) or congenital heart failure (CHF) are generally evaluated based on blood tests. AKI (also known as acute renal failure) is characterized by a relatively sudden decline in kidney function, such as over a few hours or a few days. The kidneys are important organs that are responsible not only for filtering toxins and excess water from the blood but for producing enzymes (e.g., renin) and hormones (e.g., erythropoietin), which help regulate a range of bodily functions, such as blood pressure, fluid and electrolyte balance, and red blood cell production. CHF is typically caused by structural heart defects present at birth, but the onset of symptoms (e.g., edema, fatigue, shortness of breath, rapid or irregular heartbeat, and the like) may occur over time and / or may not initially be recognized as indicative of CHF. Unfortunately, these conditions are only monitored periodically, e.g., when a patient visits a healthcare facility or laboratory and submits a blood sample. Continuous monitoring of a patient’s blood would enable these and other health conditions to be identified and addressed earlier, promoting better outcomes for patients.SUMMARY

[0004] This disclosure generally relates to a monitor having electrochemical sensors configured to detect analyte levels within an interstitial fluid layer of a patient’s skin. InAttorney Docket No. A0013164W001 aspects, the monitor includes one or more flex sensors (or flex circuits), where each flex sensor includes one or more electrodes. For example, each flex sensor may include one or more of a working electrode, a counter electrode and / or a reference electrode. In some aspects, the one or more flex sensors may include at least two working electrodes; in other aspects, the one or more flex sensors may include at least three working electrodes. Each working electrode is configured to interact with an analyte within the interstitial fluid layer and generate an electrical signal indicative of an analyte level (e.g., analyte concentration). For example, a first working electrode may be configured to detect a creatinine level, a second working electrode may be configured to detect a glucose level, and a third working electrode may be configured to detect a potassium ion level.

[0005] In practice, the one or more flex sensors of the monitor are encased in a large- gauge (small diameter) retractable needle, which is inserted through the patient’s skin and into the interstitial space. A housing of the monitor is affixed to an exterior surface of the patient’s skin and can be worn for several days or longer, during which time the monitor can be configured to continuously detect the levels of multiple analytes within the interstitial fluid layer. In this way, a patient can be monitored in any location for the risk or progression of various health conditions that ordinarily require laboratory blood tests, such as acute kidney injury (AKI) or congenital heart failure (CHF).

[0006] In an aspect, an interstitial monitor configured to detect whether a patient is suffering from an acute kidney injury (AKI) is provided. The interstitial monitor including a plurality of flex sensors configured to sense a plurality of analyte levels in interstitial fluid of the patient. The plurality of flex sensors including a first flex sensor including a first working electrode responsive to a first analyte and a second working electrode responsive to a second analyte, wherein the first working electrode and the second working electrode are amperometric electrodes. The plurality of flex sensors further comprising a second flex sensor including a third working electrode responsive to a third analyte, wherein the third working electrode is a potentiometric electrode. Further, where at least one of the first flex sensor or the second flex sensor further comprises a counter electrode or a reference electrode.

[0007] In another aspect, an interstitial monitor configured to detect a renal condition of a patient is provided. The monitor including one or more flex sensors configured toAttorney Docket No. A0013164W001 sense one or more analyte levels in interstitial fluid of the patient. The one or more flex sensors including a first working electrode responsive to a first analyte; a second working electrode responsive to a second analyte; and a third working electrode responsive to a third analyte, where at least the first working electrode and the second working electrode are positioned on a first flex sensor of the one or more flex sensors, wherein the renal condition of the patient is determined based on the first analyte, the second analyte, and the third analyte in the interstitial fluid of the patient.

[0008] In yet another aspect, a method of determining a health condition of a patient based on a plurality of analyte levels in interstitial fluid of the patient is provided. The method includes interacting, at a first working electrode of at least one flex sensor, with a first concentration of a first analyte, wherein the first working electrode is an amperometric electrode. The method further includes interacting, at a second working electrode of the at least one flex sensor, with a second concentration of a second analyte, wherein the second working electrode is a potentiometric electrode. The method further includes generating, by the first working electrode, a first electrical signal proportional to the first concentration of the first analyte, and generating, by the second working electrode, a second electrical signal proportional to the second concentration of the second analyte. Additionally, the method includes converting, by a processor, the first electrical signal to a first analyte level and the second electrical signal to a second analyte level. Based on the first analyte level and the second analyte level, the method further includes determining the health condition of the patient.

[0009] The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques described in this disclosure will be apparent from the description and drawings, and from the claims.BRIEF DESCRIPTION OF DRAWINGS

[0010] Non-limiting and non-exhaustive examples are described with reference to the following Figures.

[0011] FIGS. 1A-1C are conceptual diagrams illustrating an example system including an analyte monitor configured to measure multiple analyte levels in an interstitial fluid layer of a patient’s skin, in accordance with one or more examples described herein.Attorney Docket No. A0013164W001

[0012] FIG. 2 is a schematic diagram illustrating a first example of one or more flex sensors of an analyte monitor, in accordance with one or more examples described herein.

[0013] FIG. 3 is a schematic diagram illustrating a second example of one or more flex sensors of an analyte monitor, in accordance with one or more examples described herein.

[0014] FIG. 4 is a schematic diagram illustrating a third example of one or more flex sensors of an analyte monitor, in accordance with one or more examples described herein.

[0015] FIG. 5 is a schematic diagram illustrating a fourth example of one or more flex sensors of an analyte monitor, in accordance with one or more examples described herein.

[0016] FIG. 6 is a schematic diagram illustrating an example amperometric sensor flex, in accordance with one or more examples described herein.

[0017] FIGS. 7A-7B are schematic diagrams of example potassium potentiometric sensor flexes, in accordance with one or more examples described herein.

[0018] FIG. 8 is a block diagram illustrating an example electronics system, in accordance with one or more examples described herein.

[0019] FIG. 9 is a flowchart illustrating an example method for determining an analyte level in interstitial fluid of a patient, in accordance with one or more examples described herein.

[0020] FIG. 10 is a graph illustrating an example of in vitro operation of a monitor designed to electrochemically track glucose, potassium, and creatinine levels, in accordance with one or more examples described herein.DETAILED DESCRIPTION

[0021] This disclosure generally relates to a monitor including multiple electrochemical sensors configured to detect analyte levels of multiple analytes within an interstitial fluid layer of a patient’s skin. The monitor includes one or more flex sensors (or flex circuits), where each flex sensor includes one or more electrodes. In aspects, a flex sensor is a circuit built on a flexible substrate that includes one or more of a working electrode, a counter electrode and / or a reference electrode. For example, a flex sensor may be constructed in accordance with thin film mask techniques to form elongated thin film conductors embedded or encased between layers of a selected insulative material such as aAttorney Docket No. A0013164W001 polyimide film. Each working electrode of a flex sensor may be configured to detect an analyte, which may be the same as or different than analytes detected by other working electrodes. In some aspects, the monitor may include one or more flex sensors configured with at least two working electrodes; in other aspects, the one or more flex sensors may be configured with at least three working electrodes; and in still other aspects, the one or more flex sensors may be configured with more than three working electrodes.

[0022] To detect an analyte, a working electrode may comprise or be coated with a substance that causes, facilitates, or participates in an electrochemical reaction with an analyte. In some examples, the substance may be an enzyme (or enzymes); in other examples, the substance may be an oxidative or reductive chemical or compound. In still other examples, a working electrode may facilitate a charge separation and corresponding electrical potential proportional to a concentration of an ionic analyte. As described above, each working electrode is configured to interact with an analyte in the interstitial fluid layer to generate an electrical signal indicative of an analyte level (e.g., concentration). For example, the monitor may include one or more processors for executing one or more algorithms to convert electrical signals generated by each working electrode into corresponding analyte levels. Analyte levels of each analyte may be recorded by the monitor over time to identify changes and / or rates of change in the analyte levels. In aspects, a first working electrode may be configured to detect a creatinine level, a second working electrode may be configured to detect a glucose level, and a third working electrode may be configured to detect a potassium ion level within the interstitial fluid layer of a patient.

[0023] In practice, the one or more flex sensors of the monitor are encased in a large- gauge (small diameter) retractable needle. In aspects, the needle is inserted through the patient’s skin and into the interstitial space and then retracted, leaving the one or more flex sensors in the patient’s interstitial fluid layer. A housing of the monitor is affixed to an exterior surface of the patient’s skin and can be worn for several days or longer, during which time the monitor is configured to continuously detect the levels of multiple analytes within the interstitial fluid layer. In aspects, the monitor may be configured to detect analytes that are indicative of one or more health conditions. For example, interstitial glucose levels may be indicative of a risk and / or progression of diabetes and, combined with serum creatinine and / or serum potassium levels, interstitial glucose levels may beAttorney Docket No. A0013164W001 indicative of a risk and / or progression of AKI. Moreover, serum potassium levels may be indicative of CHF progression. In this way, by configuring the monitor to detect interstitial levels of glucose, creatinine, and / or potassium ion, a patient can be monitored for the risk and / or progression of AKI and / or CHF, which would ordinarily require laboratory blood tests.

[0024] Creatine is a naturally occurring compound in muscle cells that is involved in energy production; and creatinine is a waste product resulting from the breakdown of creatine that is excreted by the muscle cells. Ordinarily, creatinine is filtered out of the blood and released in urine by the kidneys. Serum creatinine (Scr) is a biomarker used to measure glomerular filtration rate (GFR), which is indicative of kidney function. Serum creatinine is often monitored in CHF patients to detect a decline in kidney function. Additionally, serum creatinine is an important criterion for detecting and diagnosing AKI. However, since serum creatinine is a lagging indicator of AKI, it is beneficial to identify changes in creatinine levels as they arise. Accordingly, occasional blood tests that measure Scr may be insufficient for early detection of AKI.

[0025] Blood glucose levels are also indicative of kidney function. Under normal conditions, the kidneys function to reabsorb glucose. Thus, high levels of glucose (hyperglycemia) - particularly in non-diabetic patients - can be indicative of abnormal kidney function and / or AKI. Moreover, elevated glucose levels can damage blood vessels, exacerbating the symptoms and progression of CHF as a common complication of kidney dysfunction. In fact, for patients admitted to the hospital with high baseline glucose, the risk of AKI and mortality may be almost double. In contrast, a subsequent decline in glucose level can be indicative of kidney improvement or Acute Kidney Recovery (AKR). In combination with creatinine monitoring, continuously monitoring fluctuations in blood glucose levels would be beneficial in detecting reduced kidney function associated with AKI and / or an onset or progression of CHF.

[0026] Potassium (e.g., in the form of potassium ion, K+) is another measurable biomarker that exhibits changes in interstitial concentration as kidney function deteriorates during AKI onset. As noted above, normally functioning kidneys maintain electrolyte balance within the body. For example, the hormone aldosterone acts on the kidneys to promote sodium (Na+) and water reabsorption in exchange for potassium (K+) secretion atAttorney Docket No. A0013164W001 the distal renal tubules. As kidney function declines, the Na+ / K+ ion exchange may be disrupted, altering the balance of electrolytes. In addition to being correlated with AKI, abnormal potassium levels may be indicative of a progression in CHF. Moreover, many medications used to manage CHF may cause hypokalemia (low K+) or hyperkalemia (high K+), both of which can lead to cardiac arrhythmias or even death. Indeed, high serum potassium levels, such as levels greater than or equal to 5.50 mmol / L, are associated with AKI and a significantly increased short- and long-term risk of death.

[0027] As should be appreciated, the monitor described herein enables continuous monitoring of multiple analytes that would otherwise require laboratory testing. By continuously monitoring multiple analyte levels that are indicative of one or more health conditions, the risk and / or progression of such health conditions can be better managed, leading to better patient outcomes. For example, continuous monitoring of serum creatinine, glucose, and potassium enables earlier detection and / or progression supervision of a health condition such as AKI. Early detection of AKI is particularly important as the progression from AKI onset to death can occur over a few days. Additionally, continuous monitoring of serum potassium enables better management of an existing health condition such as CHF. As should be appreciated, by configuring the monitor to detect interstitial levels of additional or different analytes, other health conditions can be detected and / or monitored without requiring laboratory blood tests.

[0028] FIGS. 1A-1C are conceptual diagrams illustrating an example system 100 including an analyte monitor 102 configured to measure multiple analyte levels in an interstitial fluid layer of a patient’s skin, in accordance with one or more examples described herein.

[0029] As illustrated by FIG. 1 A, monitor 102 includes housing 104, adhesive layer 106, and needle 108. Housing 104 encases an electronics system 110 (see FIG. 8) and is mounted by adhesive layer 106 onto an exterior surface of skin 112 of patient 114. Needle 108, which includes one or more flex sensors 116 (see FIGS. 1B-1C), extends distally from housing 104 into skin 112. In aspects, needle 108 is retractable following insertion of the one or more flex sensors 116, which are configured to remain in the interstitial fluid layer 122.Attorney Docket No. A0013164W001

[0030] Skin 112 includes multiple layers, including an epidermal layer 118, which is positioned above a dermal layer 120, which is positioned above an interstitial fluid layer 122. In some examples, dermal layer 120 may comprise at least a portion of the interstitial fluid layer 122. In addition to fluid, which includes primarily water, the interstitial fluid layer 122 includes, for example, blood cells 124 and analytes 126. In some aspects, analytes 126 may include glucose, creatinine, and / or potassium. One or more blood vessels 128 (which exchange fluids, analytes 126, blood cells 124, waste products, and the like, with the interstitial fluid layer 122) may be located within or below the interstitial fluid layer 122 and / or the dermal layer 120.

[0031] When monitor 102 is mounted on an exterior surface of skin 112, the one or more flex sensors 116 within needle 108 may be positioned subcutaneously within the interstitial fluid layer 122 and configured to measure interstitial analyte levels of multiple analytes 126, including one or more of glucose, creatinine, and / or potassium. In some aspects, an interstitial analyte level may correspond to a concentration of an analyte 126 within the interstitial fluid layer 122; in other aspects, an interstitial analyte level may correspond to another designation or measure of an analyte quantity within the interstitial fluid layer 122.

[0032] In aspects, monitor 102 may be mounted on skin 112 of patient 114 for a period of time, such as an hour, a plurality of hours, a day, a plurality of days, a week, a plurality of weeks, or any subset, combination or extension thereof. In this way, monitor 102 may be configured to periodically or continuously monitor interstitial analyte levels for multiple analytes over the period of time, enabling early detection of abnormal analyte levels, changes in analyte levels, and / or rates of change of analyte levels, for example, which can minimize delays in detecting a risk and / or progression of one or more health conditions.

[0033] FIG. IB illustrates a first bisectional view of needle 108 from a first lateral perspective (e.g., first side of needle 108), and FIG. 1C illustrates a second bisectional view of needle 108 from a second lateral perspective (e.g., second side of needle 108). As shown, a first flex sensor 116A is visible in the first bisectional view of needle 108 and a second flex sensor 116B is visible in the second bisectional view of needle 108. In aspects, the first flex sensor 116A may be loaded back-to-back with the second flex sensor 116BAttorney Docket No. A0013164W001 within a single needle 108. In some examples, first flex sensor 116A is adhered back-to- back with second sensor 116B within needle 108. In other examples, one or more electrodes may be formed on a first side of a flexible substrate and one or more electrodes may be formed on a second side of the flexible substrate, thereby configuring a single flex sensor 116 with a plurality of electrodes. In still other examples, two or more independent flex sensors 116A-B may be loaded back-to-back within needle 108. As should be appreciated, within the constraints of needle 108, any configuration of one or more flex sensors 116A-B is contemplated herein. As mentioned above, needle 108 is configured for delivering the one or more flex sensors 116 into the interstitial fluid layer 122. Following insertion, needle 108 may be retracted into monitor 102 or otherwise removed from the insertion site.

[0034] As described further with respect to FIGS. 2-5, each of the one or more flex sensors 116A-B may include one or more of a working electrode (e.g., WE 134, WE 136, WE 142), a counter electrode (e.g., CE 140), and / or reference electrode (e.g., RE 138). In general, a working electrode is configured to interact with an analyte 126 and generate an electrical signal proportional to a level or concentration of the analyte 126 in the interstitial fluid layer 122. A counter electrode is configured to complete a circuit with one or more working electrodes to enable electrical signals to flow and be measured. For example, a counter electrode may include any suitable material compatible with an electrical circuit, e.g., one or more metals including carbon, platinum, palladium, gold, silver, copper, titanium, iridium and alloys thereof. In some examples, the one or more flex sensors 116 do not include a counter electrode, which may alternatively be positioned on an exterior surface of skin 112 or otherwise electrically coupled with one or more working electrodes and electrical circuitry of electronics system 110.

[0035] A reference electrode is configured to maintain a known and stable baseline electrical signal against which electrical signal(s) generated by one or more working electrodes can be measured. In aspects, an electrical signal generated by a working electrode may be in the form of a voltage (e.g., a difference in electrical potential between two points), a current (e.g., a measure of a rate at which charge flows through a circuit), or an impedance (e.g., a measure of a resistance to current flow in a circuit). The relationship between the electrical signal and an analyte level may be represented by a formula or algorithm stored by electronics system 110. By processing the electrical signal accordingAttorney Docket No. A0013164W001 to the algorithm, the electronics system 110 converts the electrical signal into a corresponding analyte level, which can be evaluated to determine a risk and / or progression of a health condition of patient 114.

[0036] FIG. 2 is a schematic diagram illustrating a first example of one or more flex sensors 216 of a monitor 202. As described above, analyte monitor 202 (e.g., the same or similar as monitor 102 of FIG. 1A) may include one or more flex sensors 216 (e.g., the same or similar as the one or more flex sensors 116A-B of FIGS. 1B-1C). In aspects, a flex sensor is a circuit built on a flexible substrate that includes one or more of a working electrode, a counter electrode and / or a reference electrode. In aspects, when the monitor 202 is mounted on an exterior skin surface of a patient, a needle 208 (e.g., needle 108 of FIG. 1 A) encasing the one or more flex sensors 216 is configured to extend distally through the skin and into an interstitial fluid layer. The interstitial fluid layer is below the top layers of a patient’s skin but above adjacent layers of tissue. As detailed above, needle 208 is configured for delivering the one or more flex sensors 216 into the interstitial fluid layer of the patient. Following insertion, needle 208 may be retracted into monitor 202 or otherwise removed from the insertion site.

[0037] To deliver and / or maintain the one or more flex sensors 216 within the interstitial fluid layer and prevent penetration into the underlying tissue, a length of the needle 208 and / or the one or more flex sensors 216 may be limited. For example, the length may be limited to about two millimeters (2 mm) to about 4 mm. “About,” as used herein, encompasses values within 10%, 20%, or 30% percent of a stated value. Moreover, a size of the needle 208 (e.g., diameter and / or length) may be limited to prevent patient discomfort during insertion. As a result, a number of flex sensors 216 and a number of electrodes on each flex sensor may be limited by the diameter and / or length of the needle 208.

[0038] As illustrated, the one or more flex sensors 216 include a first flex sensor 216A and a second flex sensor 216B. The first flex sensor 216A includes a first proximal end 230A and a first distal end 232A, and the second flex sensor 216B includes a second proximal end 230B and a second distal end 232B. In aspects, prior to insertion into a patient’s skin, the first proximal end 230A of the first flex sensor 216A and the second proximal end 230B of the second flex sensor 216B are positioned proximally with respectAttorney Docket No. A0013164W001 to monitor 202 within needle 208. In additional aspects, the first distal end 232A of the first flex sensor 216A and the second distal end 232B of the second flex sensor 216B are positioned distal to monitor 202 within needle 208. In this way, when monitor 202 is mounted and needle 208 penetrates a patient’s skin, the first distal end 232A of the first flex sensor 216A and the second distal end 232B of the second flex sensor 216B may be delivered into the interstitial fluid layer of the patient.

[0039] Positioned at first distal end 232A of first flex sensor 216A are a plurality of electrodes (e.g., three electrodes). First flex sensor 216A includes two working electrodes and a reference electrode. The working electrodes include a creatinine working electrode (WEc) 234 (configured to detect a creatinine level in the interstitial fluid layer of the patient) and a glucose working electrode (WEg) 236 (configured to detect a glucose level in the interstitial fluid layer of the patient). In some examples, WEc 234 and WEg 236 are amperometric enzymatic sensors that incorporate enzyme layers to facilitate electrochemical reactions with an analyte (e.g., an analyte 126 of FIG. 1A). To regulate diffusion of the analyte (e.g., creatinine and / or glucose) into the enzyme layer, a limiting membrane may be applied to an exterior surface of amperometric enzyme sensors, such as WEc 234 and WEg 236. By positioning WEc 234 and WEg 236 on the same flex sensor 216A, the limiting membrane can be applied during the same manufacturing step to both electrodes, thereby simplifying manufacturing of the first flex sensor 216A.

[0040] In the illustrated example, WEc 234 is positioned proximal to WEg 236 along first flex sensor 216A; however, in other examples, WEc 234 may be positioned distal to WEg 236 along first flex sensor 216A. In some cases, WEc 234 may be less sensitive to creatinine than WEg 236 is to glucose. By positioning WEc 234 proximal to WEg 236, a length of a conductive path may be minimized between WEc 234 and an electronics system 210 of monitor 202 (e.g., the same or similar as electronics system 800 of FIG. 8), thereby minimizing resistance and potentially improving detection of electrical signals generated by WEc 234. Moreover, by increasing a size (e.g., thickness, width, surface roughness and / or length) of WEc 234, the available surface area and / or volume of WEc 234 for reacting with creatinine is increased, thereby increasing the sensitivity of WEc 234 to creatinine.Attorney Docket No. A0013164W001

[0041] Further, at first distal end 232A, the first flex sensor 216A includes a reference electrode (RE) 238 configured to maintain a known and stable baseline electrical signal against which electrical signal(s) generated by WEc 234, WEg 236, and / or a potassium working electrode (WEp) 242 of second flex sensor 216B (described further below) can be measured. As shown, RE 238 is positioned between WEc 234 and WEg 236 at first distal end 232A; however, in other examples, RE 238 may be positioned distally with respect to both WEc 234 and WEg 236 or proximally with respect to both WEc 234 and WEg 236 at first distal end 232A. As distance increases between a reference electrode and a working electrode, resistance also increases. Since signal noise is proportional to resistance, locating RE 238 between WEc 234 and WEg 236 may minimize noise associated with electrical signals generated by one or both of WEc 234 and WEg 236.

[0042] With respect to the second flex sensor 216B, the second distal end 232B includes two electrodes, a counter electrode (CEg / c) 240 (which is configured to complete circuits with WEc 234 and WEg 236) and a potassium working electrode (WEp) 242 (which is configured to detect a level of potassium ion in the interstitial fluid layer of the patient). In some aspects, WEp 242 is a potentiometric sensor, which is an electrochemical sensor that creates an electrical potential (e.g., voltage) with respect to another electrode based on a concentration of an analyte ion (e.g., potassium ion, K+) in a solution (e.g., interstitial fluid layer). In the illustrated example, CEg / c 240 is positioned proximal to WEp 242 along the second flex sensor 216B; however, in other examples, CEg / c 240 may be positioned distal to WEp 242 along the second flex sensor 216B.

[0043] As described above, a counter electrode is configured to complete a circuit with one or more working electrodes by participating in or facilitating a complementary (or reverse) reaction, thereby enabling electrical signal(s) to flow from the one or more working electrodes and be measured. However, if the counter electrode is unable to efficiently facilitate the counter reaction, e.g., due to byproduct buildup, surface saturation, etc., the counter electrode may interfere with the electrical signal(s) generated by the one or more working electrodes. To minimize such interference, CEg / c 240 may have a greater surface area than the cumulative surface area of WEc 234 and WEg 236.

[0044] In aspects, the surface area of CEg / c 240 may be increased two-dimensionally or three-dimensionally. For example, surface area may be increased two-dimensionally byAttorney Docket No. A0013164W001 increasing the width and / or length of CEg / c 240, and surface area may be increased three- dimensionally by increasing a roughness or undulation on the surface of CEg / c 240. For example, to increase roughness, CEg / c 240 may be formed of electroplated platinum, or screen-printed platinum or carbon. Based on factors associated with a particular system, the surface area of CEg / c 240 may be equal to or greater than the cumulative surface area ofWEc 234 and WEg 236.

[0045] As further illustrated, first flex sensor 216A includes first electrical circuitry 244A, which includes a first plurality of conductive paths (or wires) between the three sensor electrodes (e.g., WEc 234, WEg 236, and RE 238) and general electrodes 246A (e.g., configured for general sensor operation), which are electrically coupled to or included in electronics system 210 of monitor 202. Each electrode may be associated with one of the plurality of conductive paths, whereby the electrode is electrically coupled with an analog front end (AFE) of the electronics system 210 (see FIG. 8). As shown, since first flex sensor 216A has three sensor electrodes, first electrical circuitry 244 A includes three conductive paths (or wires) coupling the three sensor electrodes to general electrodes 246 A. Similarly, second flex sensor 216B includes second electrical circuitry 244B, which includes a second plurality of conductive paths (or wires) between the sensor electrodes (e.g., CEg / c 240 and WEp 242) and general electrodes 246B (e.g., configured for general sensor operation), which are electrically coupled to the electronics system 210. Since second flex sensor 216B has two sensor electrodes, second electrical circuitry 244B includes two conductive paths (or wires) coupling the three sensor electrodes to general electrodes 246B.

[0046] In aspects, prior to insertion into a patient’s skin, first flex sensor 216A may be loaded back-to-back with second flex sensor 216B within needle 208. For example, a first substrate layer of first flex sensor 216A may be aligned against a second substrate layer of second flex sensor 216B within needle 208. In this way, first electrical circuitry 244 A of first flex sensor 216A may be aligned against second electrical circuitry 244B of the second flex sensor 216B within needle 208. In some cases, the first substrate layer of first flex sensor 216A may be adhered (e.g., with an adhesive) to the second substrate layer of second sensor 216B and loaded into needle 208. In other cases, one or more first electrodes (e.g., electrodes WEc 234, WEg 236, and RE 238) may be formed on a first side of a flexible substrate and one or more second electrodes (e.g., CEg / c 240 and WEpAttorney Docket No. A0013164W001242) may be formed on a second side of the flexible substrate. In this way, both sides of a single flex sensor may include a plurality of electrodes (e.g., WEc 234, WEg 236, RE 238, CEg / c 240, and WEp 242). In still other examples, first flex sensor 216A and second flex sensor 216B may be independent and loaded back-to-back within needle 208. As should be appreciated, within the constraints of needle 208, the one or more flex sensors 216 may be loaded in any suitable configuration. By implementing a plurality of working electrodes on one or more flex sensors 216, monitor 202 is configured to detect interstitial analyte levels of multiple analytes (e.g., creatinine, glucose, and potassium). In this way, while monitor 202 is being worn by a patient, monitor 202 is able to continuously monitor for certain health conditions, such as AKI and CHF, without requiring laboratory testing.

[0047] FIG. 3 is a schematic diagram illustrating a second example of one or more flex sensors 316 of a monitor 302. In this example, at least second flex sensor 316B may differ from second flex sensors 216B described with respect to FIG. 2.

[0048] In aspects, when the monitor 302 is mounted on an exterior skin surface of a patient, a needle 308 encasing the one or more flex sensors 316 is configured to extend distally through the skin and into an interstitial fluid layer to deliver the one or more flex sensors 316 into the interstitial fluid layer. Following insertion, needle 308 may be retracted into monitor 302 or otherwise removed from the insertion site. To deliver and / or maintain the one or more flex sensors 316 within the interstitial fluid layer and prevent penetration into the underlying tissue, a length of the needle 308 and / or the one or more flex sensors 316 may be limited. Moreover, a size of the needle 308 (e.g., diameter and / or length) may be limited to prevent patient discomfort during insertion. As a result, a number of flex sensors 316 and a number of electrodes on each flex sensor 316 may be limited by the diameter and / or length of needle 308.

[0049] As shown in FIG. 3, the one or more flex sensors 316 include first flex sensor 316A and second flex sensor 316B. The first flex sensor 316A (e.g., the same or similar as first flex sensor 216A of FIG. 2) includes a first proximal end 330A and a first distal end 332A, and the second flex sensor 316B includes a second proximal end 330B and a second distal end 332B. In aspects, prior to insertion into a patient’s skin, the first proximal end 330A of the first flex sensor 316A and the second proximal end 330B of the second flex sensor 316B are positioned proximally with respect to monitor 302 within needle 308. InAttorney Docket No. A0013164W001 additional aspects, the first distal end 332A of the first flex sensor 316A and the second distal end 332B of the second flex sensor 316B are positioned distal to monitor 302 within needle 308. In this way, when monitor 302 is mounted and needle 308 penetrates a patient’s skin, the first distal end 332A of the first flex sensor 316A and the second distal end 332B of second flex sensor 316B may be delivered into the interstitial fluid layer of the patient (e.g., interstitial fluid layer 122 of FIG. 1A).

[0050] Similar to FIG. 2, FIG. 3 illustrates first flex sensor 316A having three electrodes, including two working electrodes and a reference electrode. The working electrodes include a creatinine working electrode (WEc) 334 (configured to detect a creatinine level in the interstitial fluid layer of the patient), a glucose working electrode (WEg) 336 (configured to detect a glucose level in the interstitial fluid layer of the patient), and a first reference electrode (RE) 338 A (configured to maintain a known and stable baseline electrical signal against which electrical signal(s) generated by WEc 334 and / or WEg 336 can be measured). In the illustrated example, WEc 334 is larger than WEg 336 and is positioned proximal to WEg 336 along first flex sensor 316A; however, in other examples, WEc 334 may be the same or similar size as WEg 336 and / or may be positioned distal to WEg 336 along first flex sensor 316A. As shown, RE 338A is positioned between WEc 334 and WEg 336; however, in other examples, the RE 338A may be positioned distal to both WEc 334 and WEg 336 or proximal to both WEc 334 and WEg 336. In some examples, WEc 334 and WEg 336 are amperometric enzymatic sensors that incorporate enzyme layers to facilitate electrochemical reactions with an analyte (e.g., creatinine and / or glucose).

[0051] Unlike FIG. 2, second flex sensor 316B of FIG. 3 may be different than second flex sensor 216B of FIG. 2. In this example, second distal end 332B of second flex sensor 316B includes three electrodes: a counter electrode, a potassium working electrode, and a reference electrode. As noted above, a size of needle 308 (e.g., diameter and / or length) and size of the one or more flex sensor 316 (e.g., thickness, width, and / or length) may be limited so as to extend into but not beyond the interstitial fluid layer and / or to promote patient comfort. Accordingly, configuring second flex sensor 316B with three electrodes rather than the two electrodes of second flex sensor 216B may result in altering a size of one or more electrodes. For example, counter electrode (CEg / c) 340, which is configured to complete circuits with WEc 334 and WEg 336, may be of a different size (e.g., differentAttorney Docket No. A0013164W001 width and / or length) than counter electrode (CEg / c) 240 of FIG. 2. As illustrated, CEg / c 340 is larger than CEg / c 240 of FIG. 2; however, in other examples, CEg / c 340 may be the same size or smaller than CEg / c 240 of FIG. 2.

[0052] As discussed above, a counter electrode is configured to complete a circuit with one or more working electrodes by participating in or facilitating a complementary (or reverse) reaction, thereby enabling electrical signal(s) to flow from the one or more working electrodes and be measured. However, if the counter electrode is unable to efficiently facilitate the counter reaction, e.g., due to byproduct buildup, surface saturation, etc., the counter electrode may interfere with the electrical signal(s) generated by the one or more working electrodes. As with CEg / c 240, to minimize such interference, CEg / c 340 may have a greater surface area than the cumulative surface area of WEc 334 and WEg 336. In aspects, the surface area of CEg / c 340 may be increased two-dimensionally or three-dimensionally, as described above with respect to CEg / c 240.

[0053] Additionally, potassium working electrode (WEp) 342, which is configured to detect a level of potassium ion in the interstitial fluid layer of the patient, may be of a different size (e.g., different width and / or length) than potassium working electrode (WEp) 242 of FIG. 2. As illustrated, WEp 342 is smaller than WEp 242; however, in other examples, WEp 342 may be the same size or larger than WEp 242. As illustrated by FIG.3, CEg / c 340 is in a proximal position with respect to WEp 342 along the second flex sensor 316B; however, in other examples, CEg / c 340 may be positioned distal to WEp 342 along the second flex sensor 316B.

[0054] Further, unlike second flex sensor 216B of FIG. 2, second flex sensor 316B of FIG. 3 includes a second reference electrode (RE) 338B. In this example, RE 338B is configured to maintain a known and stable potential against which a potential of WEp 342 can be measured. As described above, WEp 342 may be a potentiometric sensor, which is an electrochemical sensor that generates an electrical potential (e.g., voltage) based on a concentration of an analyte (e.g., potassium ion, K+) in a solution (e.g., interstitial fluid layer). To determine an accurate electrical signal corresponding to K+ concentration, a particularly stable and reliable baseline electrical signal may be beneficial. Since resistance increases with increased distance between a reference electrode and a working electrode, and signal noise is proportional to resistance, it may be beneficial to position aAttorney Docket No. A0013164W001 reference electrode (e.g., RE 338B) in close proximity to WEp 342. In one example, RE 338B may be positioned between CEg / c 340 and WEp 342 (shown); in another example, RE 338B may be positioned distal to WEp 342 (not shown). In this way, noise may be minimized with respect to electrical signal(s) (e.g., voltage) generated by WEp 342. Alternatively, RE 338B can be used as a ‘noise cancellation’ electrode or ‘working background’ electrode instead of as an additional reference electrode, e.g., as an alternate method to minimize electrical and / or chemical noise.

[0055] As further illustrated by FIG. 3, first flex sensor 316A includes first electrical circuitry 344A, which includes a first plurality of conductive paths (or wires) between the three sensor electrodes (e.g., WEc 334, WEg 336, and RE 338A) and general electrodes 346A (e.g., configured for general sensor operation), which are electrically coupled to or included in electronics system 310 of monitor 302. Each sensor electrode may be associated with one of the plurality of conductive paths, whereby the sensor electrode is electrically coupled with an analog front end (AFE) of the electronics system 310. As shown, since first flex sensor 316A has three sensor electrodes, first electrical circuitry 344A includes three conductive paths (or wires) coupling the three sensor electrodes to general electrodes 346A. Similarly, second flex sensor 316B includes second electrical circuitry 344B, which includes a second plurality of conductive paths (or wires) between the three sensor electrodes (e.g., CEg / c 340, RE 338B, and WEp 342) and general electrodes 346B (e.g., configured for general sensor operation), which are electrically coupled to or included in the electronics system 310. Since second flex sensor 316B has three sensor electrodes, second electrical circuitry 344B includes three conductive paths (or wires).

[0056] As described with reference to FIG. 2, prior to insertion into a patient’s skin, first flex sensor 316A may be loaded back-to-back with second flex sensor 316B within needle 308. For example, a first substrate layer of first flex sensor 316A may be aligned against a second substrate layer of second flex sensor 316B within needle 308. In this way, first electrical circuitry 344A of first flex sensor 316A may be aligned against second electrical circuitry 344B of second flex sensor 316B within needle 308. In some cases, the first substrate layer of first flex sensor 316A may be adhered (e.g., with an adhesive) to the second substrate layer of second sensor 316B and loaded into needle 308. In other cases, one or more first electrodes (e.g., electrodes WEc 334, RE 338A, and WEg 336) may beAttorney Docket No. A0013164W001 formed on a first side of a flexible substrate and one or more second electrodes (e.g., CEg / c 340, RE 338B, and WEp 342) may be formed on a second side of the flexible substrate. In this way, both sides of a single flex sensor may include a plurality of electrodes (e.g., WEc 334, WEg 336, RE 338A-338B, CEg / c 340, and WEp 342). In still other examples, first flex sensor 316A and second flex sensor 316B may be independent and loaded back-to-back within needle 308. As should be appreciated, within the constraints of needle 308, the one or more flex sensors 316 may be loaded in any suitable configuration. By implementing a plurality of working electrodes on one or more flex sensors 316, monitor 302 is configured to detect interstitial analyte levels of multiple analytes (e.g., creatinine, glucose, and potassium). In this way, while monitor 302 is being worn by a patient, monitor 302 is able to continuously monitor for certain health conditions, such as AKI and CHF, without laboratory testing.

[0057] FIG. 4 is a schematic diagram illustrating a third example of one or more flex sensors 416 of a monitor 402. In this example, at least second flex sensor 416B may differ from the second flex sensors 216B, 316B described with respect to FIGS. 2-3.

[0058] In aspects, when the monitor 402 is mounted on an exterior skin surface of a patient, a needle 408 encasing the one or more flex sensors 416 is configured to extend distally through the skin and into an interstitial fluid layer to deliver the one or more flex sensors 416 into the interstitial fluid layer. Following insertion, needle 408 may be retracted into monitor 402 or otherwise removed from the insertion site. As described above, to maintain the one or more flex sensors 416 within the interstitial fluid layer and prevent penetration into the underlying tissue, a length of the needle 408 and / or the one or more flex sensors 416 may be limited. Moreover, a size of the needle 408 (e.g., diameter and / or length) may be limited to prevent patient discomfort during insertion. As a result, a number of flex sensors 416 and a number of electrodes on each flex sensor 416 may be limited by the diameter and / or length of needle 408.

[0059] As shown in FIG. 4, the one or more flex sensors 416 include first flex sensor 416A and second flex sensor 416B. The first flex sensor 416A (e.g., the same or similar as first flex sensor 216A of FIG. 2 and first flex sensor 316A of FIG. 3) includes a first proximal end 430A and a first distal end 432A, and the second flex sensor 416B includes a second proximal end 430B and a second distal end 432B. In aspects, prior to insertion intoAttorney Docket No. A0013164W001 the patient’s skin, the first proximal end 430A of the first flex sensor 416A and the second proximal end 43 OB of the second flex sensor 416B are positioned proximally with respect to monitor 402 within needle 408. In additional aspects, the first distal end 432A of the first flex sensor 416A and the second distal end 432B of the second flex sensor 416B are positioned distal to monitor 402 within needle 408. In this way, when monitor 402 is mounted and needle 408 penetrates a patient’s skin, the first distal end 432A of the first flex sensor 416A and the second distal end 432B of second flex sensor 416B may be delivered into the interstitial fluid layer of the patient (e.g., interstitial fluid layer 122 of FIG. 1A).

[0060] Similar to FIGS. 2-3, FIG. 4 illustrates first flex sensor 416A having three electrodes, including two working electrodes and a reference electrode. The working electrodes include a creatinine working electrode (WEc) 434 (configured to detect a creatinine level in the interstitial fluid layer of the patient), a glucose working electrode (WEg) 436 (configured to detect a glucose level in the interstitial fluid layer of the patient), and a first reference electrode (RE) 438 A (configured to maintain a known and stable baseline electrical signal against which electrical signal(s) generated by WEc 434 and / or WEg 436 can be measured). In the illustrated example, WEc 434 is larger than and proximal to WEg 436 along first flex sensor 416A; however, in other examples, WEc 434 may be the same or similar size as WEg 436 and / or may be positioned distal to WEg 436 along first flex sensor 416A. As shown, RE 438 A is positioned between WEc 434 and WEg 436; however, in other examples, the RE 438A may be positioned distal to both WEc 434 and WEg 436 or proximal to both WEc 434 and WEg 436. In some examples, WEc 434 and WEg 436 are amperometric enzymatic sensors that incorporate enzyme layers to facilitate electrochemical reactions with an analyte (e.g., creatinine and / or glucose).

[0061] Second flex sensor 416B of FIG. 4 may be different from second flex sensor 216B of FIG. 2 and second flex sensor 316B of FIG. 3. In this example, second distal end 432B of second flex sensor 416B includes two electrodes: a potassium working electrode (WEp) 442 and a second reference electrode (RE) 438B. That is, in this example, the one or more flex sensors 416 are not configured with a counter electrode. In this case, a counter electrode may be positioned in an alternative location, for example, at or within monitor 402, associated with needle 408, or at any other suitable location for completing circuits with working electrode WEc 434 and / or WEg 436 (not shown).Attorney Docket No. A0013164W001

[0062] In aspects, WEp 442 is configured to detect a level of potassium ion in the interstitial fluid layer of the patient. In aspects, WEp 442 may be a potentiometric sensor, which is an electrochemical sensor that generates an electrical potential (e.g., voltage) based on a concentration of potassium ion (K+) in the interstitial fluid layer. To determine an accurate electrical signal corresponding to K+ concentration, a particularly stable and reliable baseline electrical signal may be beneficial. Since resistance increases with increased distance between a reference electrode and a working electrode, and signal noise is proportional to resistance, it may be beneficial to position RE 438B in close proximity to WEp 442. Additionally, as illustrated by FIG. 4, a size (e.g., thickness, width and / or length) of RE 438B may be increased. In aspects, a reference electrode with increased dimensions may enhance potential stability due to a larger electrode area, which reduces resistance and minimizes external noise interference. Additionally, a larger reference electrode volume may increase the lifetime of the reference electrode, ensuring a stable baseline electrical potential. However, increasing the electrode's thickness, rather than its area, may raise resistance and noise, while potentially extending the electrode's operational lifetime.

[0063] For example, a secondary reference electrode (e.g., RE 438 B) that is implemented specifically for a potassium sensor (e.g., WEp 442) ensures comprehensive isolation of the potassium sensor circuitry from that of other sensors within the device. This configuration achieves complete galvanic separation, thereby optimizing the signal- to-noise ratio for the potassium sensor. In further aspects, an additional reference electrode may be employed for the creatinine sensor (e.g., WEc 434), if necessary, to prevent any interference between the glucose and creatinine sensors. It is envisaged that, if desired, any working electrode (WE) within the system could be paired with its own dedicated reference electrode.

[0064] In further aspects, WEp 442 may be a different size (e.g., different width and / or length) than WEp 242 of FIG. 2 and / or WEp 342 of FIG. 3. Moreover, RE 438B may be a different size (e.g., thickness, width, and or length) than RE 338B of FIG. 3. As shown, RE 438B is in a proximal position with respect to WEp 442 along the second flex sensor 416B; however, in other examples, RE 438B may be positioned distal to WEp 442 along the second flex sensor 416B.Attorney Docket No. A0013164W001

[0065] As with first flex sensor 216A and first flex sensor 316A, first flex sensor 416A includes first electrical circuitry 444A, which includes a first plurality of conductive paths (or wires) between the three sensor electrodes (e.g., WEc 434, WEg 436, and RE 438A) and general electrodes 446 A (e.g., configured for general sensor operation), which are electrically coupled to or included in electronics system 410 of monitor 402. Since first flex sensor 416A has three sensor electrodes, first electrical circuitry 444 A includes three conductive paths (or wires) coupling the three sensor electrodes to general electrodes 446 A. Similarly, second flex sensor 416B includes second electrical circuitry 444B, which includes a second plurality of conductive paths (or wires) between the two sensor electrodes (e.g., RE 438B and WEp 442) and general electrodes 446B (e.g., configured for general sensor operation), which are electrically coupled to or included in the electronics system 410. Since second flex sensor 416B has two sensor electrodes, second electrical circuitry 444B includes two conductive paths (or wires).

[0066] As described with reference to FIG. 2 and FIG. 3, prior to insertion into the patient’s skin, first flex sensor 416A may be loaded back-to-back with second flex sensor 416B within needle 408. For example, a first substrate layer of first flex sensor 416A may be aligned against a second substrate layer of second flex sensor 416B within needle 408. In this way, first electrical circuitry 444A of first flex sensor 416A may be aligned against second electrical circuitry 444B of second flex sensor 416B within needle 408. In some cases, the first substrate layer of first flex sensor 416A may be adhered (e.g., with an adhesive) to the second substrate layer of second sensor 416B and loaded into needle 408. In other cases, one or more first electrodes (e.g., electrodes WEc 434, RE 438A, and WEg 436) may be formed on a first side of a flexible substrate and one or more second electrodes (e.g., RE 438B and WEp 442) may be formed on a second side of the flexible substrate. In this way, both sides of a single flex sensor may include a plurality of electrodes (e.g., WEc 434, WEg 436, RE 438A-438B, and WEp 442). In still other examples, first flex sensor 416A and second flex sensor 416B may be independent and loaded back-to-back within needle 408. As should be appreciated, within the constraints of needle 408, the one or more flex sensors 416 may be loaded in any suitable configuration. By implementing a plurality of working electrodes on one or more flex sensors 416, monitor 402 is configured to detect interstitial analyte levels of multiple analytes (e.g., creatinine, glucose, and potassium). In this way, while monitor 402 is being worn by aAttorney Docket No. A0013164W001 patient, monitor 402 is able to continuously monitor for certain health conditions, such as AKI and CHF, without laboratory testing.

[0067] FIG. 5 is a schematic diagram illustrating a fourth example of one or more flex sensors 516 of a monitor 502. In this example, both the first flex sensor 516A and second flex sensor 516B may differ from the one or more flex sensors described with respect to FIGS. 2-4.

[0068] In aspects, when the monitor 502 is mounted on an exterior skin surface of a patient, a needle 508 encasing the one or more flex sensors 516 is configured to extend distally through the skin and into an interstitial fluid layer to deliver the one or more flex sensors 516 into the interstitial fluid layer. Following insertion, needle 508 may be retracted into monitor 502 or otherwise removed from the insertion site. As described above, to maintain the one or more flex sensors 516 within the interstitial fluid layer and prevent penetration into the underlying tissue, a length of the needle 508 and / or the one or more flex sensors 516 may be limited. Moreover, a size of the needle 508 (e.g., diameter and / or length) may be limited to prevent patient discomfort during insertion. As a result, a number of flex sensors 516 and a number of electrodes on each flex sensor 516 may be limited by the diameter and / or length of needle 508.

[0069] As shown in FIG. 5, the one or more flex sensors 516 include first flex sensor 516A and second flex sensor 516B. The first flex sensor 516A includes a first proximal end 530A and a first distal end 532A, and the second flex sensor 516B includes a second proximal end 530B and a second distal end 532B. In aspects, prior to insertion into a patient’s skin, the first proximal end 530A of the first flex sensor 516A and the second proximal end 530B of the second flex sensor 516B are positioned proximally with respect to monitor 502 within needle 508. In additional aspects, the first distal end 532A of the first flex sensor 516A and the second distal end 532B of the second flex sensor 516B are positioned distal to monitor 502 within needle 508. In this way, when monitor 502 is mounted and needle 508 penetrates a patient’s skin, the first distal end 532A of the first flex sensor 516A and the second distal end 532B of second flex sensor 516B may be delivered into the interstitial fluid layer of the patient (e.g., interstitial fluid layer 122 of FIG. 1A).Attorney Docket No. A0013164W001

[0070] Unlike FIGS. 2-4, FIG. 5 illustrates first flex sensor 516A having seven electrodes, including three working electrodes, three counter electrodes and a reference electrode. The working electrodes include three glucose working electrodes (WEg) 534A- C (configured to detect a glucose level in the interstitial fluid layer of the patient), three counter electrodes (CEg / c) 540A-C (configured to complete circuits with WEg 536A-C and a creatinine working electrode WEc 534 of second flex sensor 516B), and a first reference electrode (RE) 538 A (configured to maintain a known and stable baseline electrical signal against which electrical signals generated by WEg 536A-C can be measured). In the illustrated example, each of CEg / c 540A-C are larger than each of WEg 536A-C. However, in other examples, CEg / c 540A-C may be the same or similar size or smaller than WEg 536A-C; and in still other examples, one or more of CEg / c 540A-C may be the same size, smaller, or larger than one or more of WEg 536A-C.

[0071] As further illustrated in this example, each of CEg / c 540A-C may be smaller than CEg / c 240 of FIG. 2 and CEg / c 340 of FIG. 3. In contrast, a combined size of CEg / c 540A-C may be larger than at least one of CEg / c 240 of FIG. 2 and CEg / c 340 of FIG. 3. As discussed above, a counter electrode is configured to complete a circuit with one or more working electrodes by participating in or facilitating a complementary (or reverse) reaction, thereby enabling electrical signal(s) to flow from the one or more working electrodes and be measured. However, if the counter electrode is unable to efficiently facilitate the counter reaction, e.g., due to byproduct buildup, surface saturation, etc., the counter electrode may interfere with the electrical signal(s) generated by the one or more working electrodes. To minimize such interference, CEg / c 540A-C may have a greater surface area than the cumulative surface area of WEg 536A-C and WEc 534. In aspects, the cumulative surface area of CEg / c 540A-C may be increased two-dimensionally or three-dimensionally, as described above with respect to CEg / c 240 of FIG. 2.

[0072] Additionally, in this example, CEg / c 540A-C are interleaved with WEg 536A- C, that is, each of CEg / c 540A-C is positioned proximal to one of WEg 536A-C along first flex sensor 416A. For example, CEg / c 540A is positioned proximal to WEg 536A, which is positioned proximal to CEg / c 540B, which is positioned proximal to WEg 536B, which is positioned proximal to CEg / c 540C, which is positioned proximal to WEg 536C. In some aspects, a smaller working electrode may respond more quickly to changes and achieve lower detection limits for trace analytes (e.g., glucose) than a larger workingAttorney Docket No. A0013164W001 electrode; moreover, the smaller surface area of a smaller working electrode may reduce a signal-to-noise ratio. By interleaving a counter electrode with each working electrode, polarization may be reduced by distributing current more evenly across the multiple working electrodes. However, due to the smaller individual surface area and increasing distance, multiple smaller counter electrodes spread across first distal end 532A may be disadvantageous to a creatinine working electrode having a proximal position along second distal end 532B of second flex sensor 516B. Accordingly, the multiple CEg / c 540A-C may be positioned in any suitable configuration with respect to one another, the multiple WEg 536A-C, and the WEc 534.

[0073] In further aspects, second flex sensor 516B of FIG. 5 may be different than second flex sensor 216B of FIG. 2, second flex sensor 316B of FIG. 3, and second flex sensor 416B of FIG. 4. In this example, second distal end 532B of second flex sensor 516B includes three electrodes: a creatinine working electrode (WEc) 534, a potassium working electrode (WEp) 542 and a second reference electrode (RE) 538B. WEc 534 may be configured to detect a creatinine level in the interstitial fluid layer of the patient). In some examples, WEc 534 and WEg 536A-C are amperometric enzymatic sensors that incorporate enzyme layers to facilitate electrochemical reactions with an analyte (e.g., an analyte 126 of FIG. 1A).

[0074] WEp 542 is configured to detect a level of potassium ion in the interstitial fluid layer of the patient. In aspects, WEp 542 may be a potentiometric sensor, which is an electrochemical sensor that generates an electrical potential (e.g., voltage) based on a concentration of analyte (e.g., potassium ion, K+) in the interstitial fluid layer. In order to determine an accurate electrical signal corresponding to K+ concentration, a particularly stable and reliable baseline electrical signal may be beneficial. Since resistance increases with increased distance between a reference electrode and a working electrode, and signal noise is proportional to resistance, it may be beneficial to position RE 538B in close proximity to WEp 542. As shown, RE 538B is positioned between WEc 534 and WEp 542 along the second flex sensor 516B; however, in other examples, RE 538B may be configured in any suitable position along the second flex sensor 516B.

[0075] As illustrated, first flex sensor 516A includes first electrical circuitry 544 A, which includes a first plurality of conductive paths (or wires) between the seven sensorAttorney Docket No. A0013164W001 electrodes (e.g., WEg 536A-C, CEg / c 540A-C, and RE 438A) and general electrodes 546A (e.g., configured for general sensor operation), which are electrically coupled to or included in electronics system 510 of monitor 502. Since first flex sensor 516A has seven sensor electrodes, first electrical circuitry 544A includes seven conductive paths (or wires) coupled to general electrodes 546 A. Similarly, second flex sensor 516B includes second electrical circuitry 544B, which includes a second plurality of conductive paths (or wires) between the three electrodes (e.g., WEc 534, RE 538B and WEp 542) and general electrodes 546B (e.g., configured for general sensor operation), which are electrically coupled to or included in electronics system 510. Since second flex sensor 516B has three electrodes, second electrical circuitry 544B includes three conductive paths (or wires).

[0076] As described with reference to FIGS. 2-4, prior to insertion into a patient’s skin, first flex sensor 516A may be loaded back-to-back with second flex sensor 516B within needle 508. For example, a first substrate layer of first flex sensor 516A may be aligned against a second substrate layer of second flex sensor 516B within needle 508. In this way, first electrical circuitry 544A of first flex sensor 516A may be aligned against second electrical circuitry 544B of second flex sensor 516B within needle 508. In some cases, the first substrate layer of first flex sensor 516A may be adhered (e.g., with an adhesive) to the second substrate layer of second sensor 516B and loaded into needle 508. In other cases, one or more first electrodes (e.g., electrodes WEg 536A-C, CE 540A-C, and RE 538 A) may be formed on a first side of a flexible substrate and one or more second electrodes (e.g., WEc 534, RE 538B and WEp 542) may be formed on a second side of the flexible substrate. In this way, both sides of a single flex sensor may include a plurality of electrodes (e.g., WEg 536A-C, CEg / c 540A-C, RE 538A-B, and WEp 542). In still other examples, first flex sensor 516A and second flex sensor 516B may be independent and loaded back-to-back within needle 508. As should be appreciated, within the constraints of needle 508, the one or more flex sensors 516 may be loaded in any suitable configuration. By implementing a plurality of working electrodes on one or more flex sensors 516, monitor 502 is configured to detect interstitial analyte levels of multiple analytes (e.g., creatinine, glucose, and potassium). In this way, while monitor 502 is being worn by a patient, monitor 502 is able to continuously monitor for certain health conditions, such as AKI and CHF, without laboratory testing.Attorney Docket No. A0013164W001

[0077] FIG. 6 is a schematic diagram illustrating an example amperometric sensor flex 600, in accordance with one or more examples described herein.

[0078] In aspects, amperometric sensor flex 600 may correspond to a creatinine working electrode (e.g., WEc 634) or a glucose working electrode (not shown) of flex sensor 616 (e.g., the same as or similar to flex sensors 116A-B, 216A, 316A, 416A, 516A- B). As described above, flex sensor 616 may be delivered into interstitial fluid 622 of a patient via a needle 608 of an interstitial analyte monitor 602. As described above, flex sensor 616 may include an electrical circuit formed on a flexible substrate 650, such as sapphire, polyimide, silicon, or the like. In some examples, a conductive adhesion layer (e.g., titanium, Ti) may be formed between the flexible substrate 650 and a conductive metal layer 654 (e.g., trace gold, Au); in other examples, conductive metal layer 654 may be formed of multiple layers (e.g., including gold and titanium, TiAu) and / or otherwise exhibit adhesive properties. In further examples, an insulation layer 656 may be formed on the metal layer 654. In aspects, the insulation layer 656 may be polyimide and include one or more openings or holes exposing the underlying metal layer 654 (e.g., formed using a mask technique during application or using etching or other technique after application). In this way, an electrode embedded in an opening in insulation layer 656 is able to contact metal layer 654.

[0079] As shown, amperometric sensor flex 600 further includes an electrode layer 658 in contact with metal layer 654. Over the electrode layer 658 is an enzyme layer 660, which is overlaid by a limiting membrane 662. In aspects, electrode layer 658 may be formed of a conductive metal that resists corrosion, such as platinum (Pt), gold (Au), or rhodium (Rh). The limiting membrane 662 may be designed to regulate an amount of analyte 626 that diffuses from a testing fluid (e.g., interstitial fluid 622) into the enzyme layer 660, thereby ensuring that an analyte concentration in the enzyme layer 660 corresponds to the analyte concentration in the interstitial fluid of the patient. In additional or alternative aspects, the limiting membrane 662 may be configured to slow an immune response by the patient and / or improve electrode stability while implanted. In aspects, the limiting membrane may be formed of one or a combination or copolymer of the following: polyethyleneimine (PEI), polyurethane (PU), poly(ethylene glycol) (PEG), cellulose acetate, polyhydroxyethylmethacrylate (pHEMA), or a physical perforated membrane of any material, such as carbon, ceramic, ablated metals, or polymers. In additional orAttorney Docket No. A0013164W001 alternative aspects, limiting membrane 662 may be a hydrogel such as poly(vinyl alcohol), poly(methylmethacrylate), phosphoryl choline-containing zwitterionic polymers.

[0080] The enzyme layer 660 may include a suspension of one or more enzymes 664 for reacting with one or more analytes 626 (e.g., creatinine or glucose, respectively). For example, when amperometric sensor flex 600 is configured to detect a creatinine level in the interstitial fluid 622, the one or more enzymes 664 may include one or more of creatinine amidohydrolase, creatine amidinohydrolase, sarcosine oxidase, and / or creatinine iminohydrolase. In aspects, an enzyme load in the enzyme layer 660 may be optimized such that it is not too low (e.g., which may inhibit sensor sensitivity and / or responsiveness due to a shortage of available enzymes 664) and not too high (e.g., which may interfere with diffusion of the analyte 626 into the enzyme layer 660). In some aspects, an enzyme load of enzymes 664 in the enzyme layer 660 of a creatinine sensor may be optimized between about two times (2x) a baseline enzyme load to about three times (3x) the baseline enzyme load. In this example, chemical reactions 678A-C facilitated by the enzymes 664 are illustrated in FIG. 6. The hydrogen peroxide released from chemical reaction 678C reacts with the surface of electrode layer 658 according to chemical reaction 680. As shown by FIG. 6, two electrons are released for each molecule of creatinine that reacts, and the electrons are conducted via metal layer 654 to electronics system 610. In aspects, the number of electrons released via reaction 680 is proportional to the analyte level (e.g., concentration) of creatinine in the interstitial fluid 622.

[0081] In contrast, when amperometric sensor flex 600 is configured to detect a glucose level in the interstitial fluid 622, the enzymes 664 may include one or more of glucose oxidase and / or glucose dehydrogenase (not shown). In this case, the chemical reaction facilitated in enzyme layer 660 to detect the glucose level, for example, may be as follows:Glucose OxidaseGlucose + O2- > Gluconic acid + H2O2, Reaction 1.

[0082] The hydrogen peroxide released from the chemical reactions occurring in the enzyme layer 660 may react with the surface of electrode layer 658 according to the following reaction:Attorney Docket No. A0013164W001H2O2— > 02+ 2H++ 2e’, Reaction 2.

[0083] As with the creatinine sensor, two electrons are released by Reaction 2. The electrons released from electrode layer 658 are conducted via the metal layer 654 to an electronics system 610 of monitor 602. In this example (not shown), the number of electrons released via Equation 2 is proportional to the analyte level (e.g., concentration) of glucose in the interstitial fluid 622.

[0084] As should be appreciated, components of amperometric sensor flex 600 are described for purposes of example and explanation and should not be considered limiting or exclusive. That is, described components may be removed, additional components may be included, and / or alternative components may be substituted without departing from the disclosure provided herein.

[0085] FIGS. 7A-7B are schematic diagrams of example potassium potentiometric sensors, in accordance with one or more examples described herein. FIG. 7A is a schematic diagram of an example potentiometric sensor flex 700 A, including potassium working electrode (WEp) 742A (e.g., the same as or similar to WEp 242, 342, 442, and / or 542), which is configured to detect a level of an analyte 726 (e.g., potassium ion, K+) in a solution (e.g., interstitial fluid 722). In some examples, a reference electrode (not shown) may be included on potentiometric sensor flex 700A. In general, a reference electrode is configured to maintain a known and stable baseline electrical signal against which electrical signal(s) generated by WEp 742A.

[0086] As illustrated, potentiometric sensor flex 700A includes flexible substrate 750 (e.g., polyimide) overlaid by a conductive metal layer 754 (e.g., trace gold, Au). In some examples, a conductive adhesion layer (e.g., titanium, Ti) may be formed between the flexible substrate layer 750 and the conductive metal layer 754; in other examples, conductive metal layer 754 may itself be formed of multiple layers (e.g., including titanium and gold, TiAu) or otherwise exhibit adhesive properties. In aspects, flexible insulation layer 756 (e.g., polyimide) may be applied over the conductive metal layer 754. In addition to flexibility, flexible insulation layer 756 may include insulative propertiesAttorney Docket No. A0013164W001 and be applied using a film mask or other application technique, for example, to create openings or holes for exposing portions of the underlying conductive metal layer 754.

[0087] In some examples, WEp 742A may include a solid-contact electrode 757 that is coated with an ion-selective membrane (ISM) 759 and embedded in flexible insulation layer 756 at one or more exposed portions, thereby enabling WEp 742Ato contact conductive metal layer 754. As illustrated by FIG. 7A, ISM 759 is applied as an overlay on an upper surface of flexible insulation layer 756; however, in other examples, ISM 759 may be fully recessed (not shown) or partially recessed into flexible insulation layer 756 (see, e.g., FIG. 7B). In aspects, conventional ion-selective potassium electrodes include an inner filling solution (e.g., a potassium chloride, KC1, solution) and an inner conducting reference (e.g., comprising silver, Ag, or silver chloride, AgCl). In contrast, the solidcontact electrode 757 described herein may be formed of a conducting polymer (e.g., poly(aniline), poly(2,3-dihydrothieno-l,4-dioxin)-poly(styrenesulfonate), and poly(pyrrole), and any derivatives thereof); a high surface area conductive carbon material (e.g., a carbon powder or paste); and / or carbon nanotubes (CNT) or vertically aligned carbon nanotubes (VCNT), for example. In this way, the need for an inner filling solution is eliminated, thereby facilitating better production scaling of WEp 742A and eliminating risks, such as filling solution leaking into the interstitial fluid of a patient.

[0088] As described above, WEp 742A includes solid-contact electrode 757, which contacts conductive metal layer 754 along a bottom surface and is overlayed with an ion- selective membrane (ISM) 759 along a top surface. ISM 759 may be a membrane infused with one or more ionophores and / or ionic sites, for example. In aspects, an ionophore is configured to interact with a particular ion (e.g., K+) in the ISM 759. For example, when a K+-selective electrode is in contact with a sample (e.g., interstitial fluid 722) containing an analyte 726 (e.g., K+), the ionophore preferentially extracts a small amount of the analyte 726 from the interstitial fluid 722 into the ISM 759, without extracting its counter ion (e.g., chloride, CE), resulting in formation of a charge separation layer and a corresponding electrical potential (often referred to as a phase boundary potential) at an interstitial fluid / ISM interface 778A (e.g., first interface). In aspects, the interstitial fluid / ISM interface 778A may comprise an upper surface of the ISM membrane 759 in contact with the interstitial fluid 722 and may further comprise at least a portion (or layer) of the ISM membrane 759 adjacent the upper surface.Attorney Docket No. A0013164W001

[0089] A change in the K+ concentration in the interstitial fluid 722 produces a change in the phase boundary potential at the interstitial fluid / ISM interface 778A, which causes the electrical potential (e.g. voltage) of electrode WEp 742Ato change. The potential of the electrode is proportional to the concentration of the target analyte 726 (e.g., K+) in the interstitial fluid 722, and can therefore be used to determine the concentration of the analyte 726 (e.g., K+) in the interstitial fluid 722.

[0090] An ionic site may be a salt wherein one component is a hydrophobic anion (e.g., tetrakis(4-chlorophenyl)borate) and another component is a hydrophilic cation (e.g., K+). The hydrophobic anion has poor solubility in the sample phase (e.g., interstitial fluid 722), but the cation has high solubility. Alternatively, an ionic site may include an anion covalently attached to the polymer ISM 759 whereas the cation (e.g., K+) is not attached. In this case, the cation is free to exchange with cations in the sample (e.g., interstitial fluid 722). In aspects, the role of the ionic sites is to prevent coextraction of K+ and any counterions (e.g., C1-) into the ISM 759.

[0091] In examples, the solid-contact electrode 757 facilitates ion-to-electron transduction either by double-layer capacitance (e.g., when comprising a high surface area conductive carbon material, CNT, or VCNT) or a redox reaction (e.g., when comprising conducting polymers), resulting in a stable phase boundary potential at an ISM / solid- contact interface 778B (e.g., second interface). In aspects, the ISM / solid-contact interface 778B may be defined at a boundary of a lower surface of the ISM 759 in contact with the top surface of the solid-contact electrode 757 and may further comprise at least a portion (or layer) of the solid-contact electrode 757 adjacent the top surface of solid-contact electrode 757 and / or at least a portion (or layer) of the ISM 759 adjacent the lower surface of ISM 759. This ensures that only the phase boundary potential at the interstitial fluid / ISM interface 778A (e.g., first interface) changes during sensor operation. In further examples, the solid-contact electrode 757 also conducts the electrical signal to conductive metal layer 754, which in turn conducts the electrical signal to an electronics system (e.g., electronics system 800 of FIG. 8) of a patient monitor (e.g., monitor 102 of FIG. 1 A).

[0092] In still further aspects, the ISM 759 may be deposited across electrodes of a field-effect transistor (FET) (or an ion-selective field-effect transistor, ISFET), embedded in a flex sensor. In this example, the FET gate may be covered by an insulating layerAttorney Docket No. A0013164W001 before the ISM 759 is deposited. When K+ interacts with the ISM 759 the surface potential at the interface changes, altering the electric field at an electrode and thus voltage across the channel. The resulting change in voltage is proportional to the concentration of K+ in the ISM 759, which is proportional to the concentration of K+ in the interstitial fluid. In some examples, integrated circuits associated with operation of the FET are imbedded in the flex sensor.

[0093] Voltametric methods may also be applied to the K+ electrode (e.g., WEp 742A-B) configurations described herein to determine the K+ concentration using two or three electrode cell configurations (e.g., including a reference electrode and / or a counter electrode). In one example, a potential sweep is applied to the ion-selective electrode relative to the reference electrode by cyclic voltammetry or square wave voltammetry. In some examples, the counter electrode for the creatinine and glucose sensors could also be used for the K+ sensor (e.g., WEp 742A-B) or a dedicated counter electrode could be used. In cyclic voltammetry, a linear potential sweep is applied to the K+ ion-selective electrode (e.g., WEp 742A-B) from a starting potential El to a final potential E2 relative to the reference electrode, followed by reversal of the potential sweep from E2 to El. This causes the K+ ion to be transferred from the sample (e.g., interstitial fluid 722) into the ion-selective membrane (ISM) 759 or transfer of the K+ ion from the ISM 759 into the sample (depending on the direction of the potential sweep). As the K+ concentration in the ISM 759 occurs, a redox reaction at the solid contact (e.g., in the case of conducting polymers) occurs, resulting in a current passing through the ion-selective electrode (e.g., WEp 742A-B) that can be measured. In some embodiments, the potential at which the maximum current flow (corresponding to ion K+ ion transfer into or out of the ISM 759) occurs can be used to determine the K+ concentration in the sample (e.g., the potential change is proportional to the K+ concentration in the interstitial fluid 722).

[0094] In another example, ion transfer stripping voltammetry can be used. In this method, an initial potential (El) is applied to the K+-selective electrode (e.g., WEp 742A-B) relative to a reference electrode for a specific time period (tl). Then, a potential sweep (e.g., linear sweep voltammetry, differential pulse voltammetry) can be applied to the ion- selective electrode (e.g., WEp 742A-B) to drive the K+ ions from the ISM 759 (ion stripping step). The current or total charge measured during the stripping step can be usedAttorney Docket No. A0013164W001 to determine the K+ concentration in the sample (e.g., current or charge are proportional to K+ concentration in the interstitial fluid 722).

[0095] In another example, electrochemical impedance spectroscopy (EIS) could be used. In this method, the ISM 759 is deposited over two interdigitated electrodes. The impedance at discrete frequencies or over a range of frequencies between the two electrodes is measured and correlated to K+ concentration in the interstitial fluid 722. When EIS is used the ISM 759 may contain ionophores and ionic sites.

[0096] Similar to FIG. 7A, FIG. 7B is a schematic diagram of an example potentiometric sensor flex 700B, including potassium working electrode (WEp) 742B (e.g., the same as or similar to WEp 242, 342, 442, 542, and / or 742A), which is configured to detect a potassium ion (K+) level in a solution (e.g., interstitial fluid 722). In some examples, a reference electrode (not shown) may be included on potentiometric sensor flex 700B. In general, a reference electrode is configured to maintain a known and stable baseline electrical signal against which electrical signal(s) generated by WEp 742B. As with FIG. 7A, potentiometric sensor flex 700B includes flexible substrate 750 (e.g., polyimide) overlaid by a conductive metal layer 754 (e.g., trace gold, Au). In some examples, a conductive adhesion layer (e.g., titanium, Ti) may be formed between the flexible substrate layer 750 and the conductive metal layer 754; in other examples, conductive metal layer 754 may itself be formed of multiple layers (e.g., including titanium and gold, TiAu) or otherwise exhibit adhesive properties. As with FIG. 7A, flexible insulation layer 756 (e.g., polyimide) is applied over the conductive metal layer 754 using a film mask or other application technique, for example, and may include insulative properties.

[0097] As with WEp 742A, WEp 742B may include a solid-contact electrode 757 that is coated with an ion-selective membrane (ISM) 759 embedded in flexible insulation layer 756 at one or more exposed portions, thereby enabling WEp 742B to contact conductive metal layer 754. As illustrated by FIG. 7B, ISM 759 is partially recessed into flexible insulation layer 756; however, in other examples, ISM 759 may be fully recessed (not shown) or applied as an overlay on an upper surface of flexible insulation layer 756 (see, e.g., FIG. 7A). Solid-contact electrode 757 may include a conducting polymer (e.g., poly(aniline), poly(2,3-dihydrothieno-l,4-dioxin)-poly(styrenesulfonate), andAttorney Docket No. A0013164W001 poly(pyrrole), and any derivatives thereof) or a high surface area conductive carbon material (e.g., carbon powder, nanotubes or paste) to facilitate ion-to-electron transduction. As described above, ISM 759 may be a membrane infused with ionophores and / or ionic sites, for example.

[0098] As illustrated by FIG. 7B, WEp 742B may also include a permeable membrane 763 overlaying ISM 759. In aspects, permeable membrane 763 may be configured to regulate a type of analyte 726 (e.g., K+) that is diffusible from interstitial fluid 722 to the ISM 759. In this way, permeable membrane 763 limits large molecules (e.g., proteins), cells, and other chemicals in the interstitial fluid 722 from reaching the ISM 759, thereby ensuring that a target analyte concentration (e.g., K+ concentration) at the permeable membrane / ISM interface 778C (e.g., third interface) corresponds to the analyte concentration in the interstitial fluid 722 of the patient. In aspects, the permeable membrane / ISM interface 778C may be defined at a boundary of a lower surface of the permeable membrane 763 in contact with an upper surface of the ISM 759 and may further comprise at least a portion (or layer) of the ISM 759 adjacent the upper surface and / or at least a portion (or layer) of the permeable membrane 763 adjacent the lower surface.

[0099] In additional or alternative aspects, the permeable membrane 763 may be configured to slow an immune response by the patient and / or improve electrode stability while implanted. In aspects, the permeable membrane 763 may be formed of one or a combination or copolymer of the following: polyethyleneimine (PEI), polyurethane (PU), polyethylene glycol) (PEG), cellulose acetate, polyhydroxyethylmethacrylate (pHEMA), or a physical perforated membrane of any material, such as carbon, ceramic, ablated metals, or polymers. In additional or alternative aspects, permeable membrane 763 may be a hydrogel such as poly(vinyl alcohol), poly(methylmethacrylate), phosphoryl choline- containing zwitterionic polymers. In aspects, permeable membrane 763 may be the same as or different from limiting membrane 662.

[0100] As should be appreciated, components of potentiometric sensor flexes 700A- 700B are described for purposes of example and explanation and should not be considered limiting or exclusive. That is, described components may be removed, additional components may be included, and / or alternative components may be substituted without departing from the disclosure provided herein.Attorney Docket No. A0013164W001

[0101] FIG. 8 is a block diagram illustrating an example electronics system 800, in accordance with one or more examples described herein. Electronics system 800 includes an analog frontend (AFE) 866, a power supply component 867, a computing component 868, and a transmission component 869. In aspects, AFE 866 may comprise or be communicatively coupled to a plurality of channels 870 for independently receiving electrical signals from multiple working electrodes (WEs), counter electrodes (CEs), and / or reference electrodes (REs) associated with the one or more flex sensors (see FIGS. 2-5). In some examples, the plurality of channels 870 may include twelve (12) channels, with four (4) WE channels, four (4) CE channels, and four (4) RE channels; in other examples, the plurality of channels 870 may include nine (9) channels, with three (3) WE channels, three (3) CE channels, and three (3) RE channels; in still other examples, the plurality of channels 870 may include fifteen (15) channels, with five (5) WE channels, five (5) CE channels, and five (5) RE channels. As should be appreciated, the plurality of channels 870 may include any suitable number and / or configuration of channels so as enable AFE 866 to receive independent electrical signals from electrodes associated with the one or more flex sensors.

[0102] In further aspects, AFE 866 may be responsible for conditioning the electrical signals received from the one or more flex sensors. For example, AFE 866 may include or be associated with amplifiers, filters, analog-to-digital converters (ADC), and / or other electronic circuitry for enhancing quality of and / or performing processing on the electrical signals. For example, AFE 866 may filter the electrical signals to remove noise, may boost weak electrical signals, may prepare the electrical signals for analog-to-digital conversion, and / or may perform analog-to-digital conversion of the electrical signals.

[0103] In some aspects, power supply component 867 may include one or more batteries. Different battery technologies may be utilized, such as lithium-based chemistries, alkaline batteries, nickel metal hydride, or the like, and different numbers of batteries may be used. Electronics system 800 provides power to electrodes via power supply component 867, e.g., via a suitable electrical interface coupling electronics system 800 to electrical circuitry (e.g., electrical circuitry 244 of FIG. 2). Alternatively, power supply component 867 may be another type of power storage device suited for a small interstitial monitor.Attorney Docket No. A0013164W001

[0104] Computing component 868 may include one or more microcontrollers (MCU) 871 (e.g., including at least one processor 876), memory 872 and, in some cases, removable memory 873 (e.g., a micro secure digital (SD) card), in examples. In some aspects, MCU 871 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 other examples, MCU 871 may include processor 876. In some examples MCU 871 may be configured to cause a specific voltage or current to be output from power supply 867 to one or more flex sensors (e.g., flex sensors 116A-B, 216A-B, 316A-B, 416A-B, 516A-B), which each include one or more electrodes such as working electrodes, counter electrodes, and / or reference electrodes, for example.

[0105] Memory 872 may be any type of memory device and may be configured to store measurements produced by processor 876, reference values for computing baselines, formulas or algorithms for converting electrical signals to analyte levels (where different formulas and / or algorithms may be stored for each analyte being tested), and / or other data used and / or produced by processor 876 and / or MCU 871. In some examples, memory 872 may further store software and / or firmware that is executable by processor 876 and / or MCU 871. In some examples, SD card 873 may backup data stored by memory 872 and / or SD card 873 may store data (e.g., processor 876 outputs) for removal and transfer to another computing device or system.

[0106] In general, processor 876 may be configured to receive a current, voltage, and / or impedance from each working electrode (e.g., WEc, WEg, WEp) of the flex sensors. As described above, each working electrode generates an electrical signal indicative of a level (e.g. a concentration) of an analyte being measured. In some cases, the working electrodes may measure the same analyte; in other examples, the working electrodes may measure different analytes. For example, a first working electrode (e.g., WEg) may generate an electrical signal indicative of a creatinine level, where the electrical signal may be a current (e.g., iSig) or a voltage measured at the first working electrode. Similarly, a second working electrode may generate an electrical signal indicative of a glucose level, where the electrical signal may be a current (e.g., iSig) or a voltage measured at the second working electrode. In further examples, a third workingAttorney Docket No. A0013164W001 electrode may generate an electrical signal indicative of a potassium level, where the electrical signal may be a voltage measured at the third working electrode.

[0107] For example, processor 876 may receive each electrical signal (e.g., a measured current, voltage, and / or impedance) after the electrical signal is measured at each working electrode (e.g., first, second, or third working electrodes above). Upon receipt of an electrical signal, processor 876 may calibrate the electrical signal utilizing one or more reference values, which are based on a known analyte quantity, e.g., a zero-analyte measurement to determine a baseline electrical signal. In some examples, reference values may be specific to the analyte being tested and may be stored, e.g., in a reference memory of memory 872 and / or SD Card 873, and retrieved by processor 876. Based on the received electrical signal and the reference values, processor 876 may determine an analyte measurement, such as an analyte level or analyte concentration in an interstitial fluid layer of a patient. In aspects, one or more algorithms or formulas may be processed by processor 876 to convert the received electrical signal into an analyte level.

[0108] Processor 876 may store the analyte measurements in memory 872 and / or SD card 873. Additionally, processor 876 and / or MCU 871 may send the analyte measurements to transmission component 869, which may be associated with a display (not shown) and / or one or more communication protocols, such as Bluetooth low energy (BLT) technologies 874, near-field communication (NFC / RFID) extensions 875, or any other suitable transmission protocol or standard.

[0109] FIG. 9 is a flowchart illustrating an example method 900 for determining a health condition of a patient based on an analyte level in interstitial fluid of a patient, in accordance with one or more examples described herein. For example, the health condition may include AKI and / or CHF. One or more of the operations of FIG. 9 may be performed using monitor 102 of FIG. 1 A, monitor 202 of FIG. 2, monitor 302 of FIG. 3, monitor 402 of FIG. 4, monitor 502 of FIG. 5, amperometric sensor flex 600, potentiometric sensor flexes 700A-700B of FIGS. 7A-7B, and / or electronics system 800 of FIG. 8. However, the disclosed monitors and sensors 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 electronics system 800 of FIG. 8.Attorney Docket No. A0013164W001

[0110] At operation 902, a power supply component (e.g., power supply component 867 of FIG. 8) of an analyte monitor (e.g., monitor 102 of FIG. 1A) may generate a reference voltage (e.g., VSET) between one or more working electrodes (e.g., a creatine working electrode and / or a glucose working electrode) and a counter electrode. In some aspects, the power supply component may generate a reference voltage between the one or more working electrodes and a reference electrode. In further aspects, the one or more working electrodes, the counter electrode, and / or the reference electrode are configured on one or more flex sensors (e.g., flex sensors 216A-B, 316A-B, 416A-B, 516A-B) and positioned in an interstitial fluid layer (e.g., interstitial fluid layer 122 of FIG. 1A) of a patient. In aspects, the one or more working electrodes may be amperometric sensors (e.g., amperometric sensor flex 600) or potentiometric sensors (e.g., potentiometric sensor flexes 700A-700B).[OHl] At operation 904, a first working electrode may interact with a first analyte in the interstitial fluid layer of the patient. In aspects, the first working electrode may be an amperometric sensor, which comprises one or more enzymes configured to facilitate chemical reactions with the first analyte (e.g., creatinine or glucose).

[0112] At operation 906, a second working electrode may interact with a second analyte (e.g., K+) in the interstitial fluid layer of the patient. In aspects, the second working electrode may be a potentiometric sensor, which is configured to facilitate a charge separation or electric potential responsive to a second analyte (e.g., potassium).

[0113] At operation 908, the first working electrode may generate a first electrical signal proportional to a first concentration of the first analyte consumed by the chemical reactions. In aspects, one or more products of the chemical reactions may react with an electrode layer (e.g., electrode layer 658 of FIG. 6) of the first working electrode to generate the first electrical signal. Since the one or more products output by the chemical reactions are limited by the first concentration of the first analyte, the magnitude or strength of the generated first electrical signal is proportional to the first concentration of the first analyte. In aspects, the first working electrode may continuously generate first electrical signals while the first working electrode is positioned in the interstitial fluid layer of a patient. In this way, changes in the first analyte level may be continuously monitored.Attorney Docket No. AOOI3 I64WOOI

[0114] At operation 910, the second working electrode may generate a second electrical signal proportional to a second concentration of the second analyte. For example, as mentioned above, an ion-selective membrane (e.g., ISM 759 of FIGS. 7A-7B) may interact with the second analyte (e.g., K+) to extract it from the interstitial fluid layer into the ISM at the interstitial fluid / ISM interface (e.g., interstitial fluid / ISM interface 778 A), without extracting the analyte’s counterion (e.g., C1-), thereby causing a phase boundary potential at the interstitial fluid / ISM interface to develop. In this way, the second electrical signal (e.g., voltage) that is generated is proportional to the second concentration of the second analyte (e.g., K+) in the interstitial fluid layer. In aspects, the second working electrode may continuously generate second electrical signals while the second working electrode is positioned in the interstitial fluid layer of a patient. In this way, changes in the second analyte level may be continuously monitored.

[0115] At operation 912, the first electrical signal generated by the first working electrode and the second electrical signal generated by the second working electrode, respectively, may be electrically communicated, e.g., via electrical circuitry of a flex sensor, to a processor (e.g., processor 876) of an electronics system of a monitor.

[0116] At operation 914, the processor may convert the first electrical signal into a first analyte level. For example, the processor may execute a first formula to convert the first electrical signal to the first analyte level. In aspects, the first formula may represent a first relationship between the first electrical signal and the first analyte level. In aspects, the first relationship may be a direct relationship such that a greater magnitude or strength of the first electrical signal may correspond to a higher first analyte level and a lower magnitude or strength of the first electrical signal may correspond to a lower first analyte level.

[0117] At operation 916, the processor may convert the second electrical signal into a second analyte level. For example, the processor may execute a second formula to convert the second electrical signal to the second analyte level. In aspects, the second formula may represent a second relationship between the second electrical signal and the second analyte level. In aspects, the second relationship may be a direct relationship such that a greater second electrical signal may correspond to a higher second analyte level and a lowerAttorney Docket No. A0013164W001 magnitude or strength of the second electrical signal may correspond to a lower second analyte level.

[0118] At operation 918, based on the first analyte level and / or the second analyte level, a health condition may be determined. For example, high serum creatinine levels (e.g., above 150 pmol / L), high serum glucose levels (e.g., above 170 mg / dL), and / or high serum potassium levels (e.g., >5.50 mmol / L) may be indicative of AKI and / or a progression in CHF.

[0119] As should be appreciated, operations 902-918 of FIG. 9 are not so limited and may be performed in a different order, some or all of operations 902-918 may be performed at the same or different times, and additional operations may be performed with operations 902-918. For example, each flex sensor of the one or more flex sensors may comprise one or more working electrodes, including two or more working electrodes, three or more working electrodes, and so on, without departing from the present disclosure.EXAMPLES

[0120] A series of tests were performed to validate the use of a monitor that includes one or more flex sensors, where each flex sensor may include a plurality of electrodes, such as working electrodes, counter electrodes, and / or reference electrodes.

[0121] FIG. 10 is a graph 1000 illustrating an example in vitro operation of a monitor (e.g., monitor 102 of FIG. 1) designed to electrochemically track glucose, potassium, and creatinine levels with the electrode layout described in FIG. 5.

[0122] A test solution of phosphate-buffered saline (PBS) at room temperature was prepared. The flex sensors (e.g., flex sensors 516A and 516B) of the monitor were introduced to the text solution at an initial time, and then analytes (e.g., analytes 126 of FIG. 1) were added in a stepwise and staggered fashion. Each analyte was tested through a normal physiological range and into an abnormal physiological range associated with AKI. In aspects, the normal physiological range for creatinine in blood is from about 50 pmol / L to about 80 pmol / L for adult females and 57 pmol / L to about 93 pmol / L for adult males, the normal physiological range for potassium in blood is from about 3.4 mmol / L toAttorney Docket No. A0013164W001 about 4.8 mmol / L, and the normal physiological range for fasting blood glucose is from about 67 mg / dL to about 93 mg / dL.

[0123] Turning to the graph, the left axis shows a voltage count in arbitrary units (AU) seen at the potassium sensor in response to changes in potassium, and the right axis shows a current count in arbitrary units (AU) seen at the glucose and creatinine sensors in response to respective changes in glucose and creatinine. Data was smoothed using a 20- point moving average (potassium and creatinine) and 10-point moving average (glucose) to eliminate erroneous electrical noise spikes.

[0124] In the illustrated example, creatinine was increased in the test solution in a stepwise fashion over a first period of about 4000 seconds (s). For example, at a first time (e.g., C-Tl) (e.g., about 8000 s), a first bolus of creatinine was delivered; at a second time (C-T2) (e.g., about 10000 s), a second bolus of creatinine was delivered; and at a third time (C-T3) (e.g., about 12000 s), a third bolus of creatinine was delivered. In aspects, the amount of creatinine delivered in each of the first, second, and third boluses was the same or different. As illustrated by FIG. 10, the creatinine sensor measured a current count (AU) over the same period (e.g., C-Tl to C-T3). In proportion to the concentration of creatinine in the test solution after each bolus, at about time C-Tl, the monitor measured a current count of about 5 AU; at about time C-T2, the monitor measured a current count of about 10 AU; and at about time C-T3, the monitor measured a current count of about 15 AU.

[0125] Similarly, potassium was increased in the test solution in a stepwise fashion over a second period of about 5000 s, the second period being after the first period. That is, in this example, potassium was increased in the test solution after creatinine was increased; however, in other examples, the increase in potassium could be performed prior to the increase in creatinine or concurrently with the increase in creatinine. As illustrated, at a first time (e.g., P-Tl) (e.g., about 12000 s) a first bolus of potassium was delivered; at a second time (P-T2) (e.g., about 13000 s), a second bolus of potassium was delivered; at a third time (P-T3) (e.g., about 14000 s), a third bolus of potassium was delivered; and at a fourth time (P-T4) (e.g., about 17000 s), a fourth bolus of potassium was delivered. In aspects, the amount of potassium delivered in each of the first, second, third, and fourth boluses was the same or different. In this example, the potassium sensor measured a voltage count in arbitrary units (AU) over the same period (e.g., P-Tl to P-T4). InAttorney Docket No. A0013164W001 proportion to the concentration of potassium in the test solution after each bolus, at about time P-Tl, the monitor measured a voltage count of about 215 AU; at about time P-T2, the monitor measured a voltage count of about 220 AU; at about time P-T3, the monitor measured a voltage count of about 223 AU; and at about time P-T4, the monitor measured a voltage count of about 230 AU.

[0126] Following the increase of the creatinine and the potassium, glucose was increased in the test solution in a stepwise fashion over a third period of about 4000 s, the third period being after the first period and the second period. That is, in this example, glucose was increased in the test solution after creatinine and potassium were increased; however, in other examples, the increase in glucose could be performed prior to the increase in creatinine and / or potassium or concurrently with the increase in creatinine and / or potassium. As illustrated, at a first time (e.g., G-Tl) (e.g., about 18000 s), a first bolus of glucose was delivered; at a second time (G-T2) (e.g., about 19000 s), a second bolus of glucose was delivered; and at a third time (G-T3) (e.g., about 21000 s), a third bolus of glucose was delivered. In aspects, the amount of glucose delivered in each of the first, second, and third boluses of glucose was the same or different. In this example, the glucose sensor measured a current count in arbitrary units (AU) over the same period (e.g., G-Tl to G-T3). In proportion to the concentration of glucose in the test solution after each bolus, at about time G-Tl, the monitor measured a current count of about 6 AU; at about time G-T2, the monitor measured a current count of about 11 AU; and at about time G-T3, the monitor measured a current count of about 16 AU.

[0127] In sum, as illustrated by FIG. 10, each sensor of the multi -el ectrode configuration described in FIG. 5 exhibited independent operation and responsiveness to a particular analyte.

[0128] The following describes aspects of the disclosure herein that may be used alone or in combination.

[0129] Example 1 : An interstitial monitor configured to detect whether a patient is suffering from an acute kidney injury (AKI), the interstitial monitor having a plurality of flex sensors configured to sense a plurality of analyte levels in an interstitial fluid of a patient, the plurality of flex sensors comprising: a first flex sensor comprising a first working electrode responsive to a first analyte and a second working electrode responsiveAttorney Docket No. A0013164W001 to a second analyte, wherein the first working electrode and the second working electrode are amperometric electrodes; and a second flex sensor comprising a third working electrode responsive to a third analyte, wherein the third working electrode is a potentiometric electrode, and wherein at least one of the first flex sensor or the second flex sensor further comprises a counter electrode or a reference electrode.

[0130] Example 2: The interstitial monitor of example 1, wherein the interstitial monitor is mounted on an exterior skin surface of the patient.

[0131] Example 3: The interstitial monitor of any one of examples 1 or 2, further comprising: a needle configured to deliver the one or more flex sensors into the interstitial fluid.

[0132] Example 4: The interstitial monitor of any one of examples 1-3, wherein the first working electrode is positioned proximally to the second working electrode along the first flex sensor of the plurality of flex sensors.

[0133] Example 5: The interstitial monitor of any one of examples 1-4, wherein the reference electrode is positioned between the first working electrode and the second working electrode along the first flex sensor.

[0134] Example 6: The interstitial monitor of any one of examples 1-5, wherein the first working electrode is responsive to creatinine and the second working electrode is responsive to glucose.

[0135] Example 7: The interstitial monitor of any one of examples 1-6, wherein at least two of the first working electrode, the second working electrode, and the third working electrode share the at least one of the counter electrode or the reference electrode.

[0136] Example 8: The interstitial monitor of any one of examples 1-7, wherein the third working electrode is responsive to potassium.

[0137] Example 9: The interstitial monitor of any one of examples 1-8, wherein the first flex sensor comprises the reference electrode, and wherein the second flex sensor comprises the counter electrode.

[0138] Example 10: The interstitial monitor of example 3, wherein the needle is retractable.Attorney Docket No. A0013164W001

[0139] Example 11 : The interstitial monitor of example 3, wherein the first flex sensor of the plurality of flex sensors and the second flex sensor of the plurality of flex sensors are positioned back-to-back within the needle for delivery into the interstitial fluid.

[0140] Example 12: An interstitial monitor configured to detect a renal condition of a patient, comprising: one or more flex sensors configured to sense one or more analyte levels in an interstitial fluid of the patient, the one or more flex sensors comprising: a first working electrode responsive to a first analyte; a second working electrode responsive to a second analyte; and a third working electrode responsive to a third analyte, wherein at least the first working electrode and the second working electrode are positioned on a first flex sensor of the one or more flex sensors, wherein the renal condition of the patient is determined based on the first analyte, the second analyte, and the third analyte in the interstitial fluid of the patient.

[0141] Example 13: The interstitial monitor of example 12, wherein the first working electrode is responsive to creatinine and the second working electrode is responsive to glucose.

[0142] Example 14: The interstitial monitor of example 12, wherein the first working electrode is responsive to creatinine and the second working electrode is responsive to potassium.

[0143] Example 15: The interstitial monitor of example 12, wherein the third working electrode is responsive to potassium, and wherein the third working electrode is positioned on one of the first flex sensor or a second flex sensor of the one or more flex sensors.

[0144] Example 16: The interstitial monitor of example 13, wherein the first working electrode interacts with a first concentration of creatinine and generates a first electrical signal proportional to the first concentration of creatinine, and wherein the second working electrode interacts with a second concentration of glucose and generates a second electrical signal proportional to the second concentration of glucose.

[0145] Example 17: The interstitial monitor of example 16, wherein the first electrical signal is converted to a creatinine level and the second electrical signal is converted to a glucose level, and wherein a health condition is detected based on the creatinine level and the glucose level.Attorney Docket No. A0013164W001

[0146] Example 18: The interstitial monitor of any one of examples 12-17, further comprising: a counter electrode, wherein the counter electrode is shared by at least two of the first working electrode, the second working electrode, or the third working electrode.

[0147] Example 19: The interstitial monitor of example 15, wherein the third working electrode generates a third electrical signal proportional to a third concentration of potassium in the interstitial fluid.

[0148] Example 20: A method of determining a health condition of a patient based on a plurality of analyte levels in interstitial fluid of the patient, comprising: interacting, at a first working electrode of at least one flex sensor, with a first concentration of a first analyte, wherein the first working electrode is an amperometric electrode; interacting, at a second working electrode of the at least one flex sensor, with a second concentration of a second analyte, wherein the second working electrode is a potentiometric electrode; generating, by the first working electrode, a first electrical signal proportional to the first concentration of the first analyte; generating, by the second working electrode, a second electrical signal proportional to the second concentration of the second analyte; converting, by a processor, the first electrical signal to a first analyte level and the second electrical signal to a second analyte level; and based on the first analyte level and the second analyte level, determining the health condition of the patient.

[0149] 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 other 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.Attorney Docket No. A0013164W001

[0150] 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.

[0151] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

1. Attorney Docket No. A0013164W001CLAIMSWhat is claimed is:

1. An interstitial monitor (102) configured to detect whether a patient is suffering from an acute kidney injury (AKI), the interstitial monitor having a plurality of flex sensors (116A-B, 216A-B, 316A-B, 416A-B, 516A-B) configured to sense a plurality of analyte levels in interstitial fluid (122) of a patient, the plurality of flex sensors comprising: a first flex sensor comprising a first working electrode (134, 136, 142) responsive to a first analyte and a second working electrode (134, 136, 142) responsive to a second analyte, wherein the first working electrode and the second working electrode are amperometric electrodes (134, 136); and a second flex sensor comprising a third working electrode (134, 136, 142) responsive to a third analyte, wherein the third working electrode is a potentiometric electrode (142), and wherein at least one of the first flex sensor or the second flex sensor further comprises a counter electrode (140) or a reference electrode (138).

2. The interstitial monitor of claim 1, wherein the interstitial monitor is mounted on an exterior skin surface of the patient.

3. The interstitial monitor of any one of claims 1 or 2, further comprising: a needle configured to deliver the plurality of flex sensors into the interstitial fluid.

4. The interstitial monitor of any one of claims 1-3, wherein the first working electrode is positioned proximally to the second working electrode along the first flex sensor of the plurality of flex sensors.

5. The interstitial monitor of any one of claims 1-4, wherein the reference electrode is positioned between the first working electrode and the second working electrode along the first flex sensor.Attorney Docket No. A0013164W0016. The interstitial monitor of any one of claims 1-5, wherein the first working electrode is responsive to creatinine and the second working electrode is responsive to glucose.

7. The interstitial monitor of any one of claims 1-6, wherein at least two of the first working electrode, the second working electrode, or the third working electrode share the at least one of the counter electrode or the reference electrode.

8. The interstitial monitor of any one of claims 1-7, wherein the third working electrode is responsive to potassium.

9. The interstitial monitor of any one of claims 1-8, wherein the first flex sensor comprises at least the reference electrode, and wherein the second flex sensor comprises at least the counter electrode.

10. The interstitial monitor of claim 3, wherein the needle is retractable.

11. The interstitial monitor of claim 3, wherein a first flex sensor of the plurality of flex sensors and the second flex sensor of the plurality flex sensors are positioned back-to- back within the needle for delivery into the interstitial fluid.

12. An interstitial monitor (102) configured to detect a renal condition of a patient, comprising: one or more flex sensors (116A-B, 216A-B, 316A-B, 416A-B, 516A-B) configured to sense a plurality of analyte levels in interstitial fluid (122) of the patient, the one or more flex sensors comprising: a first working electrode (134, 136, 142) responsive to a first analyte (126); a second working electrode (134, 136, 142) responsive to a second analyte (126); and a third working electrode (134, 136, 142) responsive to a third analyte (126), wherein at least the first working electrode and the second working electrode are positioned on a first flex sensor of the one or more flex sensors, andAttorney Docket No. A0013164W001 wherein the renal condition of the patient is determined based on the first analyte, the second analyte, and the third analyte in the interstitial fluid of the patient.

13. The interstitial monitor of claim 12, wherein the first working electrode is responsive to creatinine and the second working electrode is responsive to glucose.

14. The interstitial monitor of claim 12, wherein the third working electrode is responsive to potassium, and wherein the third working electrode is positioned on one of the first flex sensor or a second flex sensor of the one or more flex sensors.

15. A method of determining a health condition of a patient based on a plurality of analyte levels in interstitial fluid of the patient, comprising: interacting (904), at a first working electrode (134, 136, 142) of at least one flex sensor (116A-B, 216A-B, 316A-B, 416A-B, 516A-B), with a first concentration of a first analyte (126), wherein the first working electrode is an amperometric electrode (134, 136); interacting (906), at a second working electrode (134, 136, 142) of the at least one flex sensor, with a second concentration of a second analyte (126), wherein the second working electrode is a potentiometric electrode (142); generating (908), by the first working electrode, a first electrical signal proportional to the first concentration of the first analyte; generating (910), by the second working electrode, a second electrical signal proportional to the second concentration of the second analyte; converting (914, 916), by a processor, the first electrical signal to a first analyte level and the second electrical signal to a second analyte level; and based on the first analyte level and the second analyte level, determining (918) the health condition of the patient.

Images